Alzheimer Disease: Faucheux B

Dubus P, Faucheux B, Boissière F, Groppi A, Vital C, Vital A, Agid Y, Hirsch EC, Merlio JP. · Laboratoire d'Histologie-Embryologie, EA 2406 Université de Bordeaux 2, Bordeaux Cedex, 33076, France. · Exp Neurol. · Pubmed #10993689 No free full text.

Abstract: The TrkAII tyrosine kinase receptor differs from the TrkAI isoform by an insertion of six amino acids in the extracellular domain. We used RT-PCR to determine their respective distribution in rat and human brain. Only trkAII transcripts were detected in 12 rat brain regions, while both trkAI and trkAII transcripts were detected in the cerebellum and pituitary gland. In human, both trkAI and trkAII transcripts were detected in the frontal, temporal, and occipital cortex and thalamus, while only trkAI transcripts were detected in the hippocampus and cerebellum. In the caudate and putamen, trkAII transcripts were exclusively detected. Thereafter, we studied the expression of TrkA isoforms in the striatum of five patients with Alzheimer's disease (AD), four patients with non-AD dementia, seven patients with Parkinson's disease, and six paired nondemented elderly control individuals. In controls and non-AD patients, a constant expression of trkAII transcripts was detected within all striatum parts. In AD patients, a heterogeneous decrease in trkAII expression was observed in the caudate, putamen, and ventral striatum, resulting either in a drop of trkAII transcript levels or in a weak coamplification of trkAII and trkAI transcripts. The alteration of TrkAII gene expression paralleled those of choline acetyltransferase. Together with previous data, this suggests that the alteration of trk gene expression could contribute to a decrease in NGF binding sites and its protective effects on cholinergic neurons of AD patients.

Ransmayr G, Faucheux B, Nowakowski C, Kubis N, Federspiel S, Kaufmann W, Henin D, Hauw JJ, Agid Y, Hirsch EC. · Universitätsklinik für Neurologie, Anichstrasse 35, A-6020, Innsbruck, Austria. · Neurosci Lett. · Pubmed #10889341 No free full text.

Abstract: Cholinergic neurons in the basal forebrain and the upper brainstem undergo changes during aging and in dementia of the Alzheimer type, Parkinson's disease and progressive supranuclear palsy. Little is known about the effect of age on neurons in the tegmental pedunculopontine nucleus. Cholinergic neurons revealed by choline acetyltransferase immunohistochemistry were quantified in the brains of 20 subjects who died without neurological disorder between 28 and 101 years of age. A U-shaped relationship between cell counts and age was found, namely, a decrease in counts between 28 and 70, a minimum between 80 and 91 years of age, and, in four subjects aged 98-101 years counts comparable to those of subjects having died between 28 and 65 years. The findings suggest that the loss of cholinergic pedunculopontine nucleus neurons is not linear. In centenarians age-related neuronal decrease in pedunculopontine nucleus neurons may be slower or the stock of pedunculopontine nucleus neurons greater than in subjects dying earlier.

Murer MG, Boissiere F, Yan Q, Hunot S, Villares J, Faucheux B, Agid Y, Hirsch E, Raisman-Vozari R. · INSERM U289, H ôpital de la Pitié Sal pêtrière, Paris, France. · Neuroscience. · Pubmed #10336117 No free full text.

Abstract: Brain-derived neurotrophic factor is a member of the family of neuronal differentiation and survival-promoting molecules called neurotrophins. Neuronal populations known to show responsiveness to the action of brain-derived neurotrophic factor include the cholinergic forebrain, mesencephalic dopaminergic, cortical, hippocampal and striatal neurons. This fact has aroused considerable interest in the possible contribution of an abnormal brain-derived neurotrophic factor function to the aetiology and physiopathology of different neurodegenerative disorders, such as Alzheimer's disease. This report describes the cellular and regional distribution of brain-derived neurotrophic factor in post mortem control human brain and in limited regions of the brain in patients with Alzheimer's disease, as was revealed by immunohistochemistry. Brain-derived neurotrophic factor is widely expressed in the control human brain, both by neurons and glia. In neurons, brain-derived neurotrophic factor was localized in the cell body, dendrites and axons. Among the structures showing the most intense immunohistochemical labeling were the hippocampus, claustrum, amygdala, bed nucleus of the stria terminalis, septum and the nucleus of the solitary tract. In the striatum, immunoreactivity was more intense in striosomes than in the matrix. Many labeled neurons were found in the substantia nigra pars compacta. The large putatively cholinergic neurons in the basal forebrain showed no immunoreactivity. The general pattern of labeling was similar in individuals with Alzheimer's disease. Brain-derived neurotrophic factor-immunoreactive material was found in senile plaques, and some immunoreactive cortical pyramidal neurons showed neurofibrillary tangles, suggesting that brain-derived neurotrophic factor may be involved in the process of neuronal degeneration and/or compensatory mechanisms which occur in this illness.