Alzheimer Disease: Chen J

Vosler PS, Brennan CS, Chen J. · Department of Neurology, University of Pittsburgh School of Medicine, S-507, Biomedical Science Tower, Pittsburgh, PA 15213, USA. · Mol Neurobiol. · Pubmed #18686046 No free full text.

Abstract: Calpain is a ubiquitous calcium-sensitive protease that is essential for normal physiologic neuronal function. However, alterations in calcium homeostasis lead to persistent, pathologic activation of calpain in a number of neurodegenerative diseases. Pathologic activation of calpain results in the cleavage of a number of neuronal substrates that negatively affect neuronal structure and function, leading to inhibition of essential neuronal survival mechanisms. In this review, we examine the mechanistic underpinnings of calcium dysregulation resulting in calpain activation in the acute neurodegenerative diseases such as cerebral ischemia and in the chronic neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, prion-related encephalopathy, and amylotrophic lateral sclerosis. The premise of this paper is that analysis of the signaling and transcriptional consequences of calpain-mediated cleavage of its various substrates for any neurodegenerative disease can be extrapolated to all of the neurodegenerative diseases vulnerable to calcium dysregulation.

Shin TM, Isas JM, Hsieh CL, Kayed R, Glabe CG, Langen R, Chen J. · Zilhka Neurogenetic Institute, University of Southern California, Los Angeles, California 90033, USA. · Mol Neurodegener. · Pubmed #18939994 links to  free full text

Abstract: ABSTRACT: BACKGROUND: The multifunctional protein vitronectin is present within the deposits associated with Alzheimer disease (AD), age-related macular degeneration (AMD), atherosclerosis, systemic amyloidoses, and glomerulonephritis. The extent to which vitronectin contributes to amyloid formation within these plaques, which contain misfolded, amyloidogenic proteins, and the role of vitronectin in the pathophysiology of the aforementioned diseases is currently unknown. The investigation of vitronectin aggregation is significant since the formation of oligomeric and fibrillar structures are common features of amyloid proteins. RESULTS: We observed vitronectin immunoreactivity in senile plaques of AD brain, which exhibited overlap with the amyloid fibril-specific OC antibody, suggesting that vitronectin is deposited at sites of amyloid formation. Of particular interest is the growing body of evidence indicating that soluble nonfibrillar oligomers may be responsible for the development and progression of amyloid diseases. In this study we demonstrate that both plasma-purified and recombinant human vitronectin readily form spherical oligomers and typical amyloid fibrils. Vitronectin oligomers are toxic to cultured neuroblastoma and retinal pigment epithelium (RPE) cells, possibly via a membrane-dependent mechanism, as they cause leakage of synthetic vesicles. Oligomer toxicity was attenuated in RPE cells by the anti-oligomer A11 antibody. Vitronectin fibrils contain a C-terminal protease-resistant fragment, which may approximate the core region of residues essential to amyloid formation. CONCLUSION: These data reveal the propensity of vitronectin to behave as an amyloid protein and put forth the possibilities that accumulation of misfolded vitronectin may contribute to aggregate formation seen in age-related amyloid diseases.

Liu RY, Gu R, Qi XL, Chen J, Liu JL, Guan ZZ. · Department of Pathology, Guiyang Medical University, Guiyang 550004, China. · Zhonghua Bing Li Xue Za Zhi. · Pubmed #17535686 No free full text.

Abstract: OBJECTIVE: To study the influence of beta-amyloid protein (Abeta) and cholesterol on the pathological changes of Alzheimer's disease (AD) and on the expression of nicotinic acetylcholine receptor (nAChR) subunits in the brains of rats. METHOD: The rats were treated by intracerebroventricular injection of Abeta1-42 and fed with a diet containing 5% cholesterol to establish animal model of AD. The pathological changes, learning and memory, and expression of nAChRs of rats were analyzed by Bieoschowsky staining, immunohistochemistry, water-labyrinth, Western blot, and RT-PCR. RESULTS: Abeta intracerebroventricular injection induced Abeta deposition in rat brains and high-cholesterol diet resulted in hypercholesterolemia in the animals. Injection of Abeta caused a reduction of learning and memory of rats and modifications of the expression of nAChRs. Cholesterol enhanced these effects of Abeta on neuropathology and expression of nAChRs. CONCLUSIONS: Abeta can induce marked neuropathological changes, influence the learning and study ability, and modify the expression of nAChRs. Cholesterol can enhance the neurotoxicity of Abeta.

Chow N, Bell RD, Deane R, Streb JW, Chen J, Brooks A, Van Nostrand W, Miano JM, Zlokovic BV. · Socratech Research Laboratories L.L.C., Department of Neurosurgery, University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14642, USA. · Proc Natl Acad Sci U S A. · Pubmed #17215356 links to  free full text

Abstract: Cerebral angiopathy contributes to cognitive decline and dementia in Alzheimer's disease (AD) through cerebral blood flow (CBF) reductions and dysregulation. We report vascular smooth muscle cells (VSMC) in small pial and intracerebral arteries, which are critical for CBF regulation, express in AD high levels of serum response factor (SRF) and myocardin (MYOCD), two interacting transcription factors that orchestrate a VSMC-differentiated phenotype. Consistent with this finding, AD VSMC overexpressed several SRF-MYOCD-regulated contractile proteins and exhibited a hypercontractile phenotype. MYOCD overexpression in control human cerebral VSMC induced an AD-like hypercontractile phenotype and diminished both endothelial-dependent and -independent relaxation in the mouse aorta ex vivo. In contrast, silencing SRF normalized contractile protein content and reversed a hypercontractile phenotype in AD VSMC. MYOCD in vivo gene transfer to mouse pial arteries increased contractile protein content and diminished CBF responses produced by brain activation in wild-type mice and in two AD models, the Dutch/Iowa/Swedish triple mutant human amyloid beta-peptide (Abeta)-precursor protein (APP)- expressing mice and APPsw(+/-) mice. Silencing Srf had the opposite effect. Expression of SRF did not change in VSMC subjected to Alzheimer's neurotoxin, Abeta. Thus, SRF-MYOCD overexpression in small cerebral arteries appears to initiate independently of Abeta a pathogenic pathway mediating arterial hypercontractility and CBF dysregulation, which are associated with Alzheimer's dementia.

Mueller-Steiner S, Zhou Y, Arai H, Roberson ED, Sun B, Chen J, Wang X, Yu G, Esposito L, Mucke L, Gan L. · Gladstone Institute of Neurological Disease, University of California, San Francisco, 1650 Owens Street, 94158, USA. · Neuron. · Pubmed #16982417 No free full text.

Abstract: Alzheimer's disease (AD) may result from the accumulation of amyloid-beta (Abeta) peptides in the brain. The cysteine protease cathepsin B (CatB) is associated with amyloid plaques in AD brains and has been suspected to increase Abeta production. Here, we demonstrate that CatB actually reduces levels of Abeta peptides, especially the aggregation-prone species Abeta1-42, through proteolytic cleavage. Genetic inactivation of CatB in mice with neuronal expression of familial AD-mutant human amyloid precursor protein (hAPP) increased the relative abundance of Abeta1-42, worsening plaque deposition and other AD-related pathologies. Lentivirus-mediated expression of CatB in aged hAPP mice reduced preexisting amyloid deposits, even thioflavin S-positive plaques. Under cell-free conditions, CatB effectively cleaved Abeta1-42, generating C-terminally truncated Abeta peptides that are less amyloidogenic. Thus, CatB likely fulfills antiamyloidogenic and neuroprotective functions. Insufficient CatB activity might promote AD; increasing CatB activity could counteract the neuropathology of this disease.

Zhou J, Chen J, Feng Y. · Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. · J Huazhong Univ Sci Technolog Med Sci. · Pubmed #16961266 No free full text.

Abstract: The carboxyl-terminal amino acids 272-299-truncated apoE4 (delta272-299) is the main fragments of apoE4 hydrolysate in neurons. The effects of truncated-ApoE4 (delta272-299) overexpression on tau phosphorylation in cultured N2a cells were investigated. The truncated-apoE4 (delta272-299) cDNA was subcloned into pEGFP-c3 to form recombinant pEGFP-T-apoE4. pEGFP-c3, pEGFP-T-apoE4 and pEGFP-apoE4 were transfected into N2a cells respectively by lipofectamine 2000 method. After 24--48 h, tau phosphorylation was detected by Western blot assay and glycogen synthase kinase-3 (GSK-3) activity by using GSK-3 activity assay. The results showed that the overexpression of both full length-apoE4 and truncated apoE4 fragments in N2a cells induced a dramatic increase in phosphorylation of tau at Ser202 sites and the activation of GSK-3 as compared with untransfected cells, most significantly in the cells transfected with pEGFP-T-apoE4 (P < 0.05). It was concluded that in vitro overexpression of truncated-ApoE4 (delta272-299) can result in tau hyperphosphorylation in N2a cells by activating GSK-3, suggesting truncated-ApoE4 (delta272-299) might contribute the pathogenesis of Alzheimer disease.

Chen K, Iribarren P, Hu J, Chen J, Gong W, Cho EH, Lockett S, Dunlop NM, Wang JM. · Laboratory of Molecular Immunoregulation, Center for Cancer Research, NCI, National Institutes of Health, Frederick, Maryland 21702, USA. · J Biol Chem. · Pubmed #16339765 links to  free full text

Abstract: The human G-protein-coupled formyl peptide receptor-like 1 (FPRL1) and its mouse homologue mFPR2 mediate the chemotactic activity of a variety of polypeptides associated with inflammation and bacterial infection, including the 42-amino acid form of amyloid beta peptide (Abeta42), a pathogenic factor in Alzheimer disease. Because mFPR2 was inducible in mouse microglial cells by proinflammatory stimulants, such as bacterial lipopolysaccharide, a ligand for the Toll-like receptor 4 (TLR4), we investigated the role of TLR2 in the regulation of mFPR2. We found that a TLR2 agonist, peptidoglycan (PGN) derived from Gram-positive bacterium Staphylococcus aureus, induced considerable mFpr2 mRNA expression in a mouse microglial cell line and primary microglial cells. This was associated with a markedly increased chemotaxis of the cells in response to mFPR2 agonist peptides. In addition, activation of TLR2 markedly enhanced mFPR2-mediated uptake of Abeta42 by microglia. Studies of the mechanistic basis showed that PGN activates MAPK and IkappaBalpha, and the effect of PGN on induction of mFPR2 was dependent on signaling pathways via ERK1/2 and p38 MAPKs. The use of TLR2 on microglial cells by PGN was supported by the fact that N9 cells transfected with short interfering RNA targeting mouse TLR2 failed to show increased expression of functional mFPR2 after stimulation with PGN. Our results demonstrated a potentially important role for TLR2 in microglial cells of promoting cell responses to chemoattractants produced in lesions of inflammatory and neurodegenerative diseases in the brain.

Nathan C, Calingasan N, Nezezon J, Ding A, Lucia MS, La Perle K, Fuortes M, Lin M, Ehrt S, Kwon NS, Chen J, Vodovotz Y, Kipiani K, Beal MF. · Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021, USA. · J Exp Med. · Pubmed #16260491 links to  free full text

Abstract: Brains from subjects who have Alzheimer's disease (AD) express inducible nitric oxide synthase (iNOS). We tested the hypothesis that iNOS contributes to AD pathogenesis. Immunoreactive iNOS was detected in brains of mice with AD-like disease resulting from transgenic expression of mutant human beta-amyloid precursor protein (hAPP) and presenilin-1 (hPS1). We bred hAPP-, hPS1-double transgenic mice to be iNOS(+/+) or iNOS(-/-), and compared them with a congenic WT strain. Deficiency of iNOS substantially protected the AD-like mice from premature mortality, cerebral plaque formation, increased beta-amyloid levels, protein tyrosine nitration, astrocytosis, and microgliosis. Thus, iNOS seems to be a major instigator of beta-amyloid deposition and disease progression. Inhibition of iNOS may be a therapeutic option in AD.

Chen J, Zhou J, Feng Y, Wang J. · Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. · J Huazhong Univ Sci Technolog Med Sci. · Pubmed #16196280 No free full text.

Abstract: In this study, we studied the effect of glycogen synthase kinase-3 (GSK-3) overactivation on neurofilament phosphorylation in cultured cells. After N2a cells were treated with the specific inhibitor (wortmannin) of phosphoinositol-3 kinase (PI-3K) or treated with wortmannin and the specific inhibitor (LiCl) of glycogen synthase kinase-3 (GSK-3), GSK-3 activity and neurofilament phosphorylation were detected by using GSK-3 activity assay, Western blots and immunofluoresence. Our results showed that after treatment of N2a cells with wortmannin for 1 h, overactivation of GSK-3 caused a reduced staining with antibody SMI32 and an enhanced staining with antibody SMI31. When N2a cells were treated with wortmannin and LiCl, the activity of GSK-3 was reduced substantially. At the same time, the phosphorylation of neurofilament was also reduced. The study demonstrated that overactivation of GSK-3 induced hyperphosphorylation of neurofilament and suggested that in vitro overactivation of GSK-3 resulted in neurofilament hyperphosphorylation and this may be the underlying mechanism for Alzheimer's disease.

Chen J, Zhou Y, Mueller-Steiner S, Chen LF, Kwon H, Yi S, Mucke L, Gan L. · Gladstone Institute of Neurological Disease, University of California, San Francisco, California 94158, USA. · J Biol Chem. · Pubmed #16183991 links to  free full text

Abstract: Accumulating evidence suggests that neurodegeneration induced by pathogenic proteins depends on contributions from surrounding glia. Here we demonstrate that NF-kappaB signaling in microglia is critically involved in neuronal death induced by amyloid-beta (Abeta) peptides, which are widely presumed to cause Alzheimer disease. Constitutive inhibition of NF-kappaB signaling in microglia by expression of the nondegradable IkappaBalpha superrepressor blocked neurotoxicity, indicating a pivotal role for microglial NF-kappaB signaling in mediating Abeta toxicity. Stimulation of microglia with Abeta increased acetylation of RelA/p65 at lysine 310, which regulates the NF-kappaB pathway. Overexpression of SIRT1 deacetylase and the addition of the SIRT1 agonist resveratrol markedly reduced NF-kappaB signaling stimulated by Abeta and had strong neuroprotective effects. Our results support a glial loop hypothesis by demonstrating a critical role for microglial NF-kappaB signaling in Abeta-dependent neurodegeneration. They also implicate SIRT1 in this pathway and highlight the therapeutic potential of resveratrol and other sirtuin-activating compounds in Alzheimer disease.

Ge W, Cheng Y, Zhang S, Ye S, Chen J, Wang R, Li C. · Hangzhou Sanatorium of PLA, Hangzhou, 310007. · Chin Med Sci J. · Pubmed #12899395 No free full text.

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Wang XY, Chen J, Zhang JT. · Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China. · Yao Xue Xue Bao. · Pubmed #12579850 No free full text.

Abstract: AIM: To study the effect of ginsenoside Rg1 on the learning and memory impairment in mice induced by aggregated beta-AP(25-35). METHODS: Mice were administered Rg1(5, 10 mg.kg-1, i.p.) for 10 d and control mice received daily i.p. injections of saline after the intracerebroventricular injection of aggregated beta-AP(25-35). After the final treatment, passive avoidance and performance in the Morris water maze (MWM) were assessed. and the activity of cortical and hippocampal ChAT and AchE were detected after the final behavior test. RESULTS: Ginsenoside Rg1 (5, 10 mg.kg-1, i.p.) significantly ameliorated the learning and memory impairment induced by beta-AP(25-35). Rg1 (5, 10 mg.kg-1) decreased the latencies and swim distances of mice to reach a hidden platform and improved the corresponding changes in search strategies occurred in the Morris water maze, and Rg1 (10 mg.kg-1, i.p.), increased step-through latencies also. Biochemical analysis showed that Rg1 (5, 10 mg.kg-1, i.p.), prevented the cortical and hippocampal ChAT activity decline induced by beta-AP(25-35), and showed inhibition of the activity of AchE, although beta-AP(25-35) showed no effect on the cortical and hippocampal AchE activity. CONCLUSION: These data showed that ginsenoside Rg1 significantly improved the learning and memory impairment induced by beta-AP(25-35), and this effect could be attributed to its inhibition of AchE and increase of ChAT activity.

Fan P, Liu Y, Zhang Z, Liu B, Ge W, Ye S, Cheng Y, Chen J. · Apolipoprotein Research Unit, School of Basic Medicine, WCUMS, Chengdu 610040, China. · Hua Xi Yi Ke Da Xue Xue Bao. · Pubmed #12536572 No free full text.

Abstract: OBJECTIVE: To investigate the relationship of serum apolipoprotein (apo) A I, B100 and E levels and apo E polymorphism to Alzheimer's disease (AD) and multiple infarction dementia (MID) in Chinese population. METHODS: The apoE phenotypes were assayed by isoelectric focusing and immunoblotting, and apolipoproteins were determined by radial immunodiffusion assay in 75 patients with AD, 36 patients with MID and 60 control subjects. RESULTS: The frequency of apo E4 allele (epsilon 4) was significantly higher and the frequency of epsilon 2 allele was lower in AD group, compared with those in the control group (0.2333 vs 0.0666, 0.0467 vs 0.0833, P < 0.05). The frequency of epsilon 4 allele in MID group was also higher than that in the control group (0.2083 vs 0.0666, P < 0.05). The fasting serum apoA 1 and E levels in AD and MID groups were remarkably lower than those in the control group (P < 0.001 and P < 0.05). CONCLUSION: Apo E4 allele epsilon 4 was associated with AD and MID. ApoE4 might be a risk factor for AD and MID, and apo E2 might be a protective factor for AD. The serum apo A I and apoE levels were significantly decreased in patients with Alzheimer's disease and multiple infarction dementia.

Sang H, Lu Z, Li Y, Ru B, Wang W, Chen J. · Department of Cell Biology and Genetics, College of Life Science, Peking University, Beijing 100871, China. · Neurosci Lett. · Pubmed #11602330 No free full text.

Abstract: Tau is a neuronal microtubule-associated protein found predominantly in axons. Hyperphosphorylation of tau reduces the stability of microtubules, which may be a pathogenic mechanism in Alzheimer's disease. To understand the different effects between tau and glycogen synthase kinase 3beta (GSK-3beta) phosphorylated tau on the organization and stability of microtubules, we performed transfection studies on 3T3 cells using EGFP-tau (Enhanced Green Fluorescence Protein-tau) and GSK-3beta to quantify the stability of microtubules. Laser confocal microscope observation revealed that thick and thin microtubule bundles could be induced by tau and GSK-3beta phosphorylated tau. The bundles appeared either to be relatively straight or to form a ring around the circumference of the cell. Both the thick and thin microtubule bundles were resistant to colchicine-induced dissociation, with thick bundles more resistant than thin bundles. The bundles induced by GSK-3beta phosphorylated tau were sensitive to colchicine, and could be reversed by the addition of LiCl, an inhibitor of GSK-3beta.

Grodstein F, Chen J, Pollen DA, Albert MS, Wilson RS, Folstein MF, Evans DA, Stampfer MJ. · Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · J Am Geriatr Soc. · Pubmed #10894312 No free full text.

Abstract: OBJECTIVE: Accumulating biologic evidence suggests that estrogen is related to cognitive function. Several epidemiologic investigations have reported that hormone therapy may reduce the risk of Alzheimer's disease. However, fewer studies have examined the relation of postmenopausal hormone use to general cognitive function in nondemented older women. Thus, we examined the association of hormone therapy to performance on four cognitive tests among healthy participants of the Nurses' Health Study. DESIGN: Cohort study. SETTING: The Nurses' Health Study, an ongoing prospective cohort study begun in 1976. PARTICIPANTS: From the Nurses' Health Study, 2138 women aged 70-78 years. MEASUREMENTS: From 1995-1999 we administered four cognitive tests (Telephone Interview for Cognitive Status (TICS), immediate and delayed recall of the East Boston Memory Test (EBMT), and verbal fluency) by telephone. Hormone use was ascertained from biennial questionnaires beginning in 1976. Linear and logistic regression models were used to calculate multivariate-adjusted differences in scores and relative risks of a low score for never users compared to current and past hormone users. RESULTS: After adjustment for confounders, neither current nor long-term hormone users demonstrated better performance on an overall measure of cognition (TICS), or on three tests of verbal memory (immediate and delayed recall of the EBMT, immediate recall of the TICS 10-word list) than never users. On the test of verbal fluency, current hormone users scored significantly better than never users (linear regression estimate of the difference in score = 0.78 points, 95% confidence interval (CI) 0.19-0.38, P = .01 for any current use; and 0.91 points, 95% CI 0.28-1.54, P = .005 for > or = 5 years current use). Current hormone users also had a 30% decrease (RR = 0.70, 95% CI 0.45-1.09) in their risk of a low score on the test of verbal fluency. These results were similar for women taking estrogen alone and estrogen combined with a progestin. CONCLUSIONS: Verbal fluency may be enhanced among women taking postmenopausal hormones, however, there is little support for better overall cognitive function in hormone users than nonusers.

Borson S, Brush M, Gil E, Scanlan J, Vitaliano P, Chen J, Cashman J, Sta Maria MM, Barnhart R, Roques J. · Alzheimer's Disease Research Center Satellite Diagnostic Clinic and Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA. · J Gerontol A Biol Sci Med Sci. · Pubmed #10619314 No free full text.

Abstract: BACKGROUND: Disproportionate increases in dementia morbidity in ethnic minorities challenge established screening methodologies because of language and culture barriers, varying access to health services, and a relative paucity of cross-cultural data validating their use. Simple screening techniques adapted to a range of health and social service settings would accelerate dementia detection and social and health services planning for demented minority elders. METHODS: The effectiveness of the Clock Drawing Test (CDT) for dementia detection was compared with that of the Mini-Mental State Examination (MMSE) and the Cognitive Abilities Screening Instrument (CASI) in community-dwelling elders of diverse linguistic, ethnic, and educational backgrounds. Subjects (N = 295) were tested at home in their native languages (English, n = 141; another language, n = 154). An informant-based clinical dementia history and functional severity index derived from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) protocols were used to classify subjects as probably demented (n = 170), and probably not demented (n = 125). RESULTS: All tests were significantly affected by education (p < .001) but not by primary language (p > .05). Sensitivities and specificities for probable dementia were 82% and 92%, respectively, for the CDT; 92% and 92% for the MMSE; and 93% and 97% for the CASI for subjects completing each test. However, in poorly educated non-English speakers, the CDT detected demented subjects with higher sensitivity than the two longer instruments (sensitivity and specificity 85% and 94% for the CDT, 46% and 100% for the MMSE, and 75% and 95% for the CASI). Moreover less information was lost due to noncompletion of the CDT than the MMSE or CASI (severe dementia or refusal: CDT 8%, MMSE 12%, and CASI 16%). CONCLUSIONS: Overall, the CDT may be as effective as the MMSE or CASI as a first-level dementia screen for clinical use in multiethnic, multilingual samples of older adults. Its brevity (1-5 minutes), minimal language requirements, high acceptability, and lack of dependence on specialized testing materials are well adapted for screening of non-English-speaking elderly persons in settings where bilingual interpreters are not readily available and screening time is at a premium.

Gurland BJ, Wilder DE, Lantigua R, Stern Y, Chen J, Killeffer EH, Mayeux R. · Columbia University Stroud Center, Faculty of Medicine and the New York State Psychiatric Institute, New York, USA. · Int J Geriatr Psychiatry. · Pubmed #10398359 No free full text.

Abstract: BACKGROUND: Rates of dementia may vary among ethnoracial groups. Any real and substantial such difference would merit serious attention by health planners, clinicians and those seeking to advance our understanding of the etiology of this group of disorders. METHODS: Randomly selected elderly persons from each of three ethnoracial groups (Latinos, African-Americans, non-Latino Whites) residing in a geographic area of northern Manhattan in New York City were screened for dementia and assessed with respect to functioning in daily tasks and other qualities of life. Systematic samples of each group were clinically evaluated for presence and subtype of dementia. Subjects were reassessed at an average of 18 months following the baseline interview. RESULTS: Age-specific prevalence of dementia was found to be higher in Latinos and African-Americans than in non-Latino Whites; incidence rates were consistent with this finding. Ethnoracial groups did not vary in the proportion of dementias diagnosed as Alzheimer's disease. Prevalence differences between ethnoracial groups remained consistent as diagnostic criteria were varied in breadth and when the possible mislabelling of depression was taken into account. However, level of education was strongly associated with rates of dementia and, when age and education were simultaneously controlled, the ethnoracial differences in rates were not consistently found. CONCLUSIONS: Planning for the wide range of services necessary for care of those suffering from dementia should take into account ethnoracial differences in rates. The higher rates found in Latino and African-American groups, relative to non-Latino Whites, are associated with clear and substantial functional dependencies and hence have important implications for qualities of life and service needs.