Alzheimer Disease: Berr C

Berr C, Akbaraly TN, Nourashemi F, Andrieu S. · Inserm, U888, Université Montpellier 1, Montpellier (34). · Presse Med. · Pubmed #17560760 No free full text.

Abstract: Dementia is a major public health problem and its burden will increase in the 30 years to come. Prevalence increases with age and incidence is slightly higher in women than men, especially after the age of 80 years. Survival after the onset of dementia is approximately 5 years. Lifestyle and health habits are a keystone for dementia: risk factors include physical, intellectual and social activity and nutritional habits. Data from well-conducted intervention studies are necessary to show whether better care for hypertension, diabetes, and dyslipidemia might decrease the incidence of dementia.

Gillette Guyonnet S, Abellan Van Kan G, Andrieu S, Barberger Gateau P, Berr C, Bonnefoy M, Dartigues JF, de Groot L, Ferry M, Galan P, Hercberg S, Jeandel C, Morris MC, Nourhashemi F, Payette H, Poulain JP, Portet F, Roussel AM, Ritz P, Rolland Y, Vellas B. · Service de Medecine Interne et de Gerontologie Clinique, Pavillon J.P. Junod, Centre Hospitalier Universitaire La Grave-Casselardit, Toulouse cedex 9, France. · J Nutr Health Aging. · Pubmed #17435956 No free full text.

Abstract: Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Meta analyses should be developed, and on the basis of their results the most appropriate interventional studies can be planned. These studies must control for the greatest number of known confounding factors and take into account the impact of the standard social determinants of food habits, such as the regional cultures, social status, and educational level.

Akwa Y, Allain H, Bentue-Ferrer D, Berr C, Bordet R, Geerts H, Nieoullon A, Onteniente B, Vercelletto M. · INSERM U488, Le Kremlin-Bicêtre, France. · Alzheimer Dis Assoc Disord. · Pubmed #16327350 No free full text.

Abstract: Neurodegenerative diseases and, in particular, Alzheimer disease, are characterized by progressive neuronal loss correlated in time with the symptoms of the disease considered. Whereas the symptoms of those incapacitating diseases are beginning to be managed with a relative efficacy, the ultimate objective of therapy nonetheless remains preventing cell (neuronal and/or astrocytic) death in a neurocytoprotective approach. In biologic terms, in the light of progress at basic research level, three strategies may be envisaged: (1) antagonizing the cytotoxic causal events (excess intracellular calcium, accumulation of abnormal proteins, excitotoxic effects of amino acids, oxidative stress, processes related to inflammation, etc.); (2) stimulating the endogenous protective processes (anti-free radical or DNA repair systems, production of neurotrophic factors, potential cytoprotective action of steroids, etc.); (3) promoting damaged structure repair strategies (grafts) or deep brain or cortical neurostimulation with a view to triggering (beyond the symptomatic actions) potential 'protective' cell mechanisms. The clinical transition of the various strategies whose efficacy is being tested in animal and/or cell models, experimental analogs of the diseases, and thus the objective demonstration in humans of pharmacological and/or surgical neurocytoprotection, is currently the subject of considerable methodological debate (What are the right psychometric assessment criteria? What are the most pertinent laboratory or neuroradiological markers, etc.?). A number of clinical trials have been completed or are ongoing with drugs that are reputed to be neuroprotective. Thus, elements of the response are beginning to be generated with a view to determining whether it will soon be possible to effectively slow or even stop the neurodegenerative process whose etiology, in most cases, remains obscure.

Ancelin ML, Berr C. · Inserm E 361, Hôpital La Colombière, Montpellier. · Psychol Neuropsychiatr Vieil. · Pubmed #15683960 No free full text.

Abstract: Although there are plausible biological mechanisms for a neuroprotective effect of estrogens, most therapeutic trials conducted to date have been unable to conclude that hormone replacement therapy (HRT) could significantly slow down the progression of Alzheimer's disease or decrease the severity of dementia. On the other hand, four meta-analyses of the principal epidemiological studies conducted to date suggested a 29 to 44% decreased risk of developing Alzheimer's disease among HRT users. Nevertheless, the results of the recent blind controlled trial, "Women's health initiative memory study" (WHIMS) including 4532 postmenopausal women indicate a two-fold increase in dementia after 4.2 years of treatment. These results do not allow to definitively conclude as to whether HRT could prevent or not the risk of developing dementia. There are several reasons for that, including the heterogeneity of the population studied and of the HRT protocols and also the presence of several methodological limitations. Furthermore, most therapeutic trials could probably not be adapted to detect a neuroprotective effect of HRT (if any). It is also probably the case for the WHIMS considering (i) the population studied (women at cardiovascular risk, aged 65 years and older, very far from the menopause and thus from both the usual clinical situation and the critical period where one might expect a neuroprotective effect to occur), and (ii) the duration and the type of HRT (oral Premarin + medroxyprogesterone, whose side-effects could be extensive, whose neuroprotective properties are not recognized) which is not representative of the clinical practice relating to HRT in France (generally natural steroids, e.g. estradiol [transdermal] + progesterone).On the basis of the data of the literature, there is currently no reason to propose HRT for the prevention of Alzheimer's disease.

Berr C. · Hospital da Salpêtrière, Paris. · Servir. · Pubmed #12035166 No free full text.

This publication has no abstract.

Le Goff M, Helmer C, Foubert-Samier A, Cowppli-Bony P, Berr C, Dartigues JF. · Inserm U897 et Université Victor-Segalen Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux cedex, France. · C R Biol. · Pubmed #19304268 No free full text.

Abstract: It is necessary to develop the prevention of Alzheimer's disease, because of the increase in the number of cases and unavailability of a curative treatment. From the data of the cohort PAQUID, we studied the risk of dementia according to leisure activities and the age of cessation of professional activity. The practice of a sport and reading decreases by 25% the risk of dementia during 15 years. The age of cessation of professional activity is not associated with the risk of dementia. An active life seems to be a possible way to prevent dementia.

Mahieux F, Onen F, Berr C, Volteau M, Habert MO, Legrain S, Dubois B, Anonymous00017. · INSERM U610 and AP-HP Fédération de Neurologie, Hôpital de la Salpétrière, Paris, France. · J Nutr Health Aging. · Pubmed #19151903 No free full text.

Abstract: OBJECTIVES: The aim of the Pre-Al study is to evaluate and compare the predictive value of different tools for an early identification of Alzheimer's disease. DESIGN AND PARTICIPANTS: Patients coming for consultation to memory clinics without dementia were included if they had an objective memory or attention trouble assessed by a MMSE score > 25 (with at least one missing item at the words recall) and / or an Isaac set test score < 28. All were examined by a neuropsychological battery (Free and Cued Selective Reminding Test, digit ordering test, WAIS-R digit symbol, Trail making test, Benton visual retention test, verbal fluency, confrontation naming and Baddeley's double task test). A subpopulation received an MRI and SPECT assessment. RESULTS AND DISCUSSION: 251 patients were included (mean age: 72.0 years; mean education duration: 10.9 years). Validation of the predictive tests will be based on the comparison of these tests in patients developing dementia and others, after a follow-up of at least 3 years. This paper presents methodology of the study and the population description.

Gillette Guyonnet S, Abellan Van Kan G, Andrieu S, Aquino JP, Arbus C, Becq JP, Berr C, Bismuth S, Chamontin B, Dantoine T, Dartigues JF, Dubois B, Fraysse B, Hergueta T, Hanaire H, Jeandel C, Lagleyre S, Lala F, Nourhashemi F, Ousset PJ, Portet F, Ritz P, Robert P, Rolland Y, Sanz C, Soto M, Touchon J, Vellas B. · Gerontopole, Pole Geriatrie Gerontologie, Hopital La Grave-Casselardit, Toulouse. · J Nutr Health Aging. · Pubmed #18810298 No free full text.

Abstract: Alzheimer's disease (AD) is the most frequent form of dementia and according to the most recent estimation it affects nearly 27 million people in the world. The onset of the disease is generally insidious. It is becoming increasingly evident that the underlying pathophysiological mechanisms are active long before the appearance of the clinical symptoms of the disease. In the current context, it is important to develop strategies to delay the onset of cognitive decline. Delaying the onset by 5 years would reduce the prevalence by half at term, and a delay of 10 years would reduce it by three-quarters. The effectiveness of currently suggested preventive approaches remains to be confirmed, but certain strategies could be applied straight away to at-risk subjects. We propose that a health-promoting memory consultation should be set up for elderly persons who have attended a specialized memory consultation and in whom the diagnosis of dementia and of AD in particular, has not been established by standardized tools. Through this consultation, they would be offered full multidimensional investigation of all aspects of their health status, follow-up could be organized, general practitioners in private practice could be made more conscious of this population and the elderly could be made more aware of the risk factors to which they are exposed. The development of an information policy for the elderly would meet a present need. In our reflection, we must take into account the question of how to give this preventive consultation its due place in the healthcare pathway of the elderly person in order to ensure coordinated follow-up with all the other health professionals involved. The principle of the health-promoting memory consultation is undergoing validation in a large French multicentre preventive trial in 1200 frail elderly persons aged 70 years followed for three years, the Multidomain Alzheimer Preventive Trial (MAPT).

Robert PH, Berr C, Volteau M, Bertogliati-Fileau C, Benoit M, Guerin O, Sarazin M, Legrain S, Dubois B, Anonymous00075. · Centre Mémoire de Ressources et de Recherche, CHU de Nice, INSERM JE 2441, Nice, France. · Am J Geriatr Psychiatry. · Pubmed #18757769 No free full text.

Abstract: OBJECTIVE: Apathy is one of the most common behavioral symptoms in mild cognitive impairment (MCI). The aim of the authors' study was to examine the influence of the apathy dimensions, i.e., emotional blunting, lack of initiative, and lack of interest, on the risk of developing of Alzheimer disease (AD) in patients with MCI. DESIGN: Longitudinal study. SETTING: Fourteen French memory clinics. PARTICIPANTS: Apathy was assessed in 214 MCI patients. The main endpoint considered was the development of AD during the 3-year follow-up. MEASUREMENTS: The neuropsychiatric evaluation included the Goldberg anxiety scale and the Montgomery and Asberg Depression Rating Scale; apathy was assessed with the Apathy Inventory. RESULTS: After 3 years, 59 patients (27.2%) had developed AD. The risk of conversion to AD was significantly higher for patients with lack of interest. Using Cox analyses, controlling for age, gender and education, the difference between survival curves was significant for lack of interest. CONCLUSIONS: Lack of interest, a mild behavioral sign, could be an indicator of potential decline in MCI patients and underlines the importance of checking the cognitive status of these patients.

Bruandet A, Richard F, Tzourio C, Berr C, Dartigues JF, Alpérovitch A, Amouyel P, Helbecque N. · INSERM, U744, Lille, France. · J Alzheimers Dis. · Pubmed #18431000 No free full text.

Abstract: The purpose of this study was to examine the impact of two polymorphisms (rs4291A>T and rs4343G>A) in the ACE gene on the risk of Alzheimer's disease (AD), using a population-based cohort of 9294 subjects selected from the electoral rolls of three French cities (the Three-City Study). Two follow-up examinations took place 2 and 4 years after inclusion. Diagnosis of dementia was assessed at baseline and at each follow-up examination by neurologists independent of the 3C Study group. For the present analysis, subjects whose mother tongue was not French, those from abroad and those lost at follow-up were excluded, leaving a sample of 6791 subjects. 108 subjects were demented at baseline and 216 subjects, among which 141 had AD, developed a dementia during follow-up. The genotype distributions of the ACE SNPs rs4291 and rs4343 did not differ according to cognitive status. After adjustment for confounding variables, the risk of developing AD was similar whatever the genotype (rs4291 AT vs TT: OR=0.90, p=0.65; AA vs TT: OR=1.05, p= 0.84; rs4343 GA vs GG: OR=1.15, p= 0.48; AA vs GG: OR=1.25, p= 0.37). No global haplotype effect could be observed on the risk of AD.

Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alpérovitch A. · INSERM, U593, University Victor Segalen Bordeaux 2, case 11, 146 rue Léo-Saignat, F-33076 Bordeaux cedex, France. · Neurology. · Pubmed #17998483 No free full text.

Abstract: BACKGROUND: Dietary fatty acids and antioxidants may contribute to decrease dementia risk, but epidemiologic data remain controversial. The aim of our study was to analyze the relationship between dietary patterns and risk of dementia or Alzheimer disease (AD), adjusting for sociodemographic and vascular risk factors, and taking into account the ApoE genotype. METHODS: A total of 8,085 nondemented participants aged 65 and over were included in the Three-City cohort study in Bordeaux, Dijon, and Montpellier (France) in 1999-2000 and had at least one re-examination over 4 years (rate of follow-up 89.1%). An independent committee of neurologists validated 281 incident cases of dementia (including 183 AD). RESULTS: Daily consumption of fruits and vegetables was associated with a decreased risk of all cause dementia (hazard ratio [HR] 0.72, 95% CI 0.53 to 0.97) in fully adjusted models. Weekly consumption of fish was associated with a reduced risk of AD (HR 0.65, 95% CI 0.43 to 0.994) and all cause dementia but only among ApoE epsilon 4 noncarriers (HR 0.60, 95% CI 0.40 to 0.90). Regular use of omega-3 rich oils was associated with a decreased risk of borderline significance for all cause dementia (HR 0.46, 95% CI 0.19 to 1.11). Regular consumption of omega-6 rich oils not compensated by consumption of omega-3 rich oils or fish was associated with an increased risk of dementia (HR 2.12, 95% CI 1.30 to 3.46) among ApoE epsilon 4 noncarriers. CONCLUSION: Frequent consumption of fruits and vegetables, fish, and omega-3 rich oils may decrease the risk of dementia and Alzheimer disease, especially among ApoE epsilon 4 noncarriers.

Sarazin M, Berr C, De Rotrou J, Fabrigoule C, Pasquier F, Legrain S, Michel B, Puel M, Volteau M, Touchon J, Verny M, Dubois B. · INSERM U 610 and Centre des Maladies Cognitives et Comportementales, Hôpital de la Salpêtrière, Paris, France. · Neurology. · Pubmed #17984454 No free full text.

Abstract: OBJECTIVE: To compare the power of tests assessing different cognitive domains for the identification of prodromal Alzheimer disease (AD) among patients with mild cognitive impairment (MCI). BACKGROUND: Given the early involvement of the medial temporal lobe, a precocious and specific pattern of memory disorders might be expected for the identification of prodromal AD. METHODS: A total of 251 patients with MCI were tested at baseline by a standardized neuropsychological battery, which included the Free and Cued Selective Recall Reminding Test (FCSRT) for verbal episodic memory; the Benton Visual Retention Test for visual memory; the Deno 100 and verbal fluency for language; a serial digit learning test and the double task of Baddeley for working memory; Wechsler Adult Intelligence Scale (WAIS) similarities for conceptual elaboration; and the Stroop test, the Trail Making test, and the WAIS digit symbol test for executive functions. The patients were followed at 6-month intervals for up to 3 years in order to identify those who converted to AD vs those who remained stable over time. Statistical analyses were based on receiver operating characteristic curve and Cox proportional hazards models. RESULTS: A total of 59 subjects converted to AD dementia. The most sensitive and specific test for diagnosis of prodromal AD was the FCSRT. Significant cutoff for the diagnosis was 17/48 for free recall, 40/48 for total recall, and below 71% for index of sensitivity of cueing (% of efficacy of semantic cues for retrieval). CONCLUSIONS: The amnestic syndrome of the medial temporal type, defined by the Free and Cued Selective Recall Reminding Test, is able to distinguish patients at an early stage of Alzheimer disease from mild cognitive impairment non-converters.

Bensemain F, Hot D, Ferreira S, Dumont J, Bombois S, Maurage CA, Huot L, Hermant X, Levillain E, Hubans C, Hansmannel F, Chapuis J, Hauw JJ, Schraen S, Lemoine Y, Buée L, Berr C, Mann D, Pasquier F, Amouyel P, Lambert JC. · INSERM, U744, Institut Pasteur de Lille, Université de Lille 2, Lille, France. · Mol Psychiatry. · Pubmed #17893704 No free full text.

Abstract: To more rapidly identify candidate genes located within chromosomal regions of interest defined by genome scan studies in Alzheimer's disease (AD), we have developed a customized microarray containing all the ORFs (n=2741) located within nine of these regions. Levels of gene expression were assessed in total RNA from brain tissue of 12 controls and 12 AD patients. Of all genes showing differential expression, we focused on the ornithine transcarbamylase (OTC) gene on Xp21.1., a key enzyme of the urea cycle which we found to be expressed in AD brains but not in controls, as confirmed by RT-PCR. We also detected mRNA expression of all the other urea cycle enzymes in AD brains. Immunochemistry experiments revealed that the OTC expression was strictly restricted to vascular endothelial cells in brain. Furthermore, OTC activity was 880% increased in the CSF of probable AD cases compared with controls. We analysed the association of the OTC -389 G/A and -241 A/G promoter polymorphisms with the risk of developing AD. We observed that rare haplotypes may be associated with the risk of AD through a possible modulation of the methylation of the OTC promoter. In conclusion, our results suggest the involvement of a new pathway in AD brains involving the urea cycle.

Boddaert J, Kinugawa K, Lambert JC, Boukhtouche F, Zoll J, Merval R, Blanc-Brude O, Mann D, Berr C, Vilar J, Garabedian B, Journiac N, Charue D, Silvestre JS, Duyckaerts C, Amouyel P, Mariani J, Tedgui A, Mallat Z. · Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Cardiovasculaire Lariboisière, Paris, France. · Am J Pathol. · Pubmed #17322377 links to  free full text

Abstract: Lactadherin is a secreted extracellular matrix protein expressed in phagocytes and contributes to the removal of apoptotic cells. We examined lactadherin expression in brain sections of patients with or without Alzheimer's disease and studied its role in the phagocytosis of amyloid beta-peptide (Abeta). Cells involved in Alzheimer's disease, including vascular smooth muscle cells, astrocytes, and microglia, showed a time-related increase in lactadherin production in culture. Quantitative analysis of the level of lactadherin showed a 35% reduction in lactadherin mRNA expression in the brains of patients with Alzheimer's disease (n = 52) compared with age-matched controls (n = 58; P = 0.003). Interestingly, lactadherin protein was detected in the brains of patients with Alzheimer's disease and controls, with low expression in areas rich in senile plaques and marked expression in areas without Abeta deposition. Using surface plasmon resonance, we observed a direct protein-protein interaction between recombinant lactadherin and Abeta 1-42 peptide in vitro. Lactadherin deficiency or its neutralization using specific antibodies significantly prevented Abeta 1-42 phagocytosis by murine and human macrophages. In conclusion, lactadherin plays an important role in the phagocytosis of Abeta 1-42 peptide, and its expression is reduced in Alzheimer's disease. Alterations in lactadherin production/function may contribute to the initiation and/or progression of Alzheimer's disease.

Robert PH, Berr C, Volteau M, Bertogliati C, Benoit M, Sarazin M, Legrain S, Dubois B, Anonymous00781. · Centre Mémoire de Ressources et de Recherche, CHU de Nice, INSERM JE 2441, France. · Clin Neurol Neurosurg. · Pubmed #16567037 No free full text.

Abstract: OBJECTIVE: To evaluate the relation between apathy and development of dementia in patients with amnestic mild cognitive impairment (MCI). METHODS: Two hundred and fifty-one French-speaking outpatients fulfilling the criteria of amnestic MCI were enrolled. Apathy was assessed with the Apathy Inventory (IA). Neuropsychiatric evaluation also included the Goldberg anxiety scale and the Montgomery and Asberg Depressive Rating Scale (MADRS). The main end point considered after a 1-year follow-up was the development of dementia of Alzheimer type (DAT). RESULTS: At baseline there were 86 (39.8%) subjects presenting at least one symptom of apathy among the 216 included in analysis. After a 1-year follow-up, 22 patients developed DAT. Of the patients with apathy at baseline 13 (15.1%) developed DAT in comparison with 9 (6.9%) of the non-apathetic patients. At the 1-year follow-up, patients developing DAT had a significantly higher frequency of apathetic symptoms (91.7%) than patients without DAT (26.9%). CONCLUSION: Taking into account that apathy is one of the most frequently observed neuropsychiatric symptoms in MCI and in DAT the present study suggests that patients with MCI and apathy should be more closely observed.

Sarazin M, Stern Y, Berr C, Riba A, Albert M, Brandt J, Dubois B. · INSERM U 610 and Fédération de Neurologie, Centre de Neuropsychologie, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75013 Paris, France. · Neurology. · Pubmed #15781821 No free full text.

Abstract: OBJECTIVE: To determine whether specific cognitive deficits can predict the progression of Alzheimer disease (AD). METHODS: Two hundred fifty-two patients with AD enrolled in the Predictors Study were followed at 6-month intervals for up to 4.5 years with neurologic, cognitive, and psychiatric examinations. Neuropsychological functions were assessed by the Modified Mini-Mental State Examination (mMMSE). Items of mMMSE were divided into five cognitive domains: temporospatial orientation, short-term memory, long-term memory, language, and visuoconstructive functions. Loss of autonomy was assessed by both the Dependency Scale (DS) and the Equivalent Institutional Care (EIC) rating. Cox proportional hazards models, adjusted for age, sex, estimated duration of illness at entry into the study, and presence of extrapyramidal signs and behavioral disturbances, were used to determine the predictive value of each neuropsychological domain on dependency outcomes. RESULTS: Global mMMSE, temporospatial orientation, and short-term memory scores were associated with a greater relative risk of moderate or severe dependency. The visuoconstructive score predicted the development of severe dependency. Long-term memory and language scores were not predictive of the EIC or DS endpoints. CONCLUSIONS: The presence of certain neuropsychological deficits at a patient's initial visit, such as short-term memory, temporospatial orientation, and constructive apraxia, predict more rapid dependency in patients with Alzheimer disease. Neuropsychological items have different weights in term of predictive power, and these effects are independent of the influence of age and disease duration at baseline.

Berr C, Richard MJ, Gourlet V, Garrel C, Favier A. · INSERM U360, Recherches epidémiologique en neurologie et psychopathologie, Hôpital de la Salpêtrière, Paris, France. · Eur J Epidemiol. · Pubmed #15074569 No free full text.

Abstract: We studied whether primary enzymatic antioxidant protection should influence cognitive decline (CD) in subjects aged 62-72 years volunteers in the Etude du Vieillissement Antériel (EVA) cohort. At baseline, we measured red blood cells activities of two enzymes: cytoplasmic form of superoxide dismutase (CuZn-SOD) and seleno dependent glutathione peroxidase (GSH-Px). During the 4 year-follow up (follow-up rate of 81%), a drop of at least 3 points in MMSE score was observed in 71 subjects (7.2%) defining individuals with CD+ among the 980 individuals. Initial GSH-Px activity appeared to be significantly lower in individual CD+ (41.2 +/- 10.3 U/g Hb vs. 44.4 +/- 9.4 in CD-, p = 0.008). Conversely, there was an increase of CuZn-SOD activity in CD+ subjects (1.13 +/- 0.10 U/mg Hb vs. 1.10 +/- 0.10, p = 0.05). Taking into account the ratio between these two levels suggest that the equilibrium between these two enzymes, an important determinant of oxidative stress level, is associated with CD. These results are independent of other potential risk factors for CD (education, Apolipoprotein E, hypertension) and suggest that this primary enzymatic system could be related to CD during aging.

Berr C, Lambert JC, Sazdovitch V, Amouyel P, Chartier-Harlin MC, Mohr M, Heldt N, Kiesmann M, Hauw JJ. · INSERM U360, Recherches Epidémiologiques en Neurologie et Psychopathologie, Hôpital de La Salpêtrière, 75651 Cedex 13, Paris, France. · Neurobiol Aging. · Pubmed #11182472 No free full text.

Abstract: We studied whether ApoE and -219 GT (ApoE promoter) polymorphism modulates neurofibrillary tangle (NFT) and senile plaque (SP) development in aging among 190 non-institutionalized individuals (mean age 79.5 years). Analysis revealed that the mean Braak stage was higher in epsilon4 allele carriers. Once individuals with Braak stage V were excluded (n = 5), relationships between NFT and the two genotypes studied were weak, whereas in epsilon4 allele carriers, the risk of SP was multiplied by 4 to 7 in four areas (CA1, subiculum, isocortex and entorhinal cortex). This association was more pronounced in subjects under 80 years and was also observed when analysis was restricted to Braak stages 0, I and II. Epsilon 2 allele carriers appeared to have fewer lesions but, due to limited numbers, this trend was not significant. In two regions (CA1, subiculum), the number of SP increased significantly for individuals who were homozygous for the T allele of -219 GT. However the association was no longer significant when controlling for ApoE epsilon4. It should be noted that the brain of elderly subjects carrying one epsilon4 allele may not undergo senile changes.

Amouyel P, Richard F, Berr C, David-Fromentin I, Helbecque N. · INSERM U508, Institut Pasteur de Lille, France. · Ann N Y Acad Sci. · Pubmed #10818534 No free full text.

Abstract: Recent reports sustain the hypothesis of tight links between vascular and neurodegenerative diseases: associations between atherosclerosis lesions and Alzheimer's disease (AD), increased risk of AD for hypertensive subjects, decreased risk of dementia for elderly treated with hypotensive drugs, and a major impact of apolipoprotein E polymorphism, a protein of the lipid metabolism, on the occurrence of AD. All these results suggest that vascular determinants, both environmental and genetic, may predispose to or speed up dementia. As a major player of vascular homeostasis, the renin angiotensin system (RAS) proteins constitute an interesting source of candidate genes. Among these, the angiotensin I-converting enzyme gene (ACE), a central enzyme of the RAS, presents in its sequence a deletion (D)/insertion (I) polymorphism associated with variations of plasma ACE levels and with the risk of myocardial infarction. We explored the impact of this genetic polymorphism on the risk of cognitive impairment and of dementia in several epidemiological studies. Physiopathological hypotheses suggest a possible involvement of the RAS proteins in the occurrence and evolution of AD. Moreover, although inconsistent, several results of case-control studies tend to suggest that the ACE I/D genetic polymorphism may constitute a genetic susceptibility factor for dementia, reinforcing the hypothesis of a major implication of vascular risk factors in the occurrence of dementia.

Lambert JC, Chartier-Harlin MC, Cottel D, Richard F, Neuman E, Guez D, Legrain S, Berr C, Amouyel P, Helbecque N. · Service d'Epidémiologie et de Santé Publique - INSERM U.508, Institut Pasteur de Lille, 1 rue Calmette, F-59019 Lille Cedex, France. · Neurogenetics. · Pubmed #10369887 No free full text.

Abstract: LDL-related protein receptor (LRP) is the main receptor in the brain for apolipoprotein E. Moreover, the LRP gene is located on chromosome 12, the site of a potential Alzheimer's disease (AD) locus. We explored the association between the LRP gene and AD in 600 French Caucasian patients (37.8% men, mean age 72.0+/-8.0 years, mean age at onset 68.7+/-8.1 years) and age-matched controls (n=646, 37.0% men, mean age 72.5+/-8.2 years) and observed an association between a (TTTC) repeat at the 3' end of an Alu sequence in the LRP gene and the risk of developing AD. Three alleles were detected in this population [corresponding to 83, 87, and 91 base pairs (bp)], the 91-bp allele being associated with an increased risk of developing AD [all patients: odds ratio (OR) 1.6, P<0.01; late-onset AD: OR 1.8, P<0.01]. This suggests an association between the LRP locus and AD. However, in the light of studies related to the exon 3 LRP polymorphism and given the low strength of the association reported here, a biologically active variant may exist on chromosome 12, either in the LRP gene itself or in another gene in the vicinity.