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[The lesions of Alzheimer's disease: which therapeutic perspectives?].
Bull Acad Natl Med. 2008 Feb; 192(2):303-18; discussion 318-21.BA

Abstract

The brain lesions associated with Alzheimer's disease are caused by extracellular accumulation of Abeta peptide and intracellular accumulation of tau protein. Abeta peptide makes the core of the senile plaque (the "focal deposit"); it is also present in the extracellular "diffuse deposits" and in the vessel walls. Neurofibrillary tangles, and neuropil threads are composed of hyperphosphorylated tau that also accumulates in the processes of the corona of the senile plaque. The Abeta deposits first involve the neocortex, while the tau pathology is initially found in the hippocampal region. Abeta deposits first occur in the neocortex, while intracellular tau accumulation mainly affect the hippocampal region. Abeta peptide deposits are initially found in all the neocortical areas, then involve the hippocampus and the subcortical nuclei. Tau lesions successively involve the hippocampal regions, multi- and uni-modal areas and finally the primary cortices in stereotyped stages. Mutations of APP, the precursor of Abeta peptide, cause autosomal dominant familial Alzheimer disease, suggesting that a cascade of reactions link Abeta overproduction, tau pathology and the clinical phenotype. Transgenic mice bearing the mutated human APP gene (APP mice) develop A deposits. Systemic injection of Abeta peptide prevents the deposition of Abeta peptide. However, a clinical trial had to be interrupted when meningoencephalitis occurred in a significant proportion of treated patients. Post mortem studies showed a relative scarcity of Abeta deposits. Forthcoming immunotherapy studies should soon show whether the prevention of Abeta deposition interrupts disease progression.

Authors+Show Affiliations

Laboratoire de Neuropathologie Raymond Escourolle, Groupe Hospitalier Pitié-Salpêtrière, 75651 Paris. charles.duyckaerts@psl.aphp.frNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Review

Language

fre

PubMed ID

18819685

Citation

Duyckaerts, Charles, et al. "[The Lesions of Alzheimer's Disease: Which Therapeutic Perspectives?]." Bulletin De l'Academie Nationale De Medecine, vol. 192, no. 2, 2008, pp. 303-18; discussion 318-21.
Duyckaerts C, Perruchini C, Lebouvier T, et al. [The lesions of Alzheimer's disease: which therapeutic perspectives?]. Bull Acad Natl Med. 2008;192(2):303-18; discussion 318-21.
Duyckaerts, C., Perruchini, C., Lebouvier, T., & Potier, M. C. (2008). [The lesions of Alzheimer's disease: which therapeutic perspectives?]. Bulletin De l'Academie Nationale De Medecine, 192(2), 303-18; discussion 318-21.
Duyckaerts C, et al. [The Lesions of Alzheimer's Disease: Which Therapeutic Perspectives?]. Bull Acad Natl Med. 2008;192(2):303-18; discussion 318-21. PubMed PMID: 18819685.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [The lesions of Alzheimer's disease: which therapeutic perspectives?]. AU - Duyckaerts,Charles, AU - Perruchini,Claire, AU - Lebouvier,Thibaud, AU - Potier,Marie-Claude, PY - 2008/9/30/pubmed PY - 2008/11/15/medline PY - 2008/9/30/entrez SP - 303-18; discussion 318-21 JF - Bulletin de l'Academie nationale de medecine JO - Bull Acad Natl Med VL - 192 IS - 2 N2 - The brain lesions associated with Alzheimer's disease are caused by extracellular accumulation of Abeta peptide and intracellular accumulation of tau protein. Abeta peptide makes the core of the senile plaque (the "focal deposit"); it is also present in the extracellular "diffuse deposits" and in the vessel walls. Neurofibrillary tangles, and neuropil threads are composed of hyperphosphorylated tau that also accumulates in the processes of the corona of the senile plaque. The Abeta deposits first involve the neocortex, while the tau pathology is initially found in the hippocampal region. Abeta deposits first occur in the neocortex, while intracellular tau accumulation mainly affect the hippocampal region. Abeta peptide deposits are initially found in all the neocortical areas, then involve the hippocampus and the subcortical nuclei. Tau lesions successively involve the hippocampal regions, multi- and uni-modal areas and finally the primary cortices in stereotyped stages. Mutations of APP, the precursor of Abeta peptide, cause autosomal dominant familial Alzheimer disease, suggesting that a cascade of reactions link Abeta overproduction, tau pathology and the clinical phenotype. Transgenic mice bearing the mutated human APP gene (APP mice) develop A deposits. Systemic injection of Abeta peptide prevents the deposition of Abeta peptide. However, a clinical trial had to be interrupted when meningoencephalitis occurred in a significant proportion of treated patients. Post mortem studies showed a relative scarcity of Abeta deposits. Forthcoming immunotherapy studies should soon show whether the prevention of Abeta deposition interrupts disease progression. SN - 0001-4079 UR - https://www.unboundmedicine.com/medline/citation/18819685/[The_lesions_of_Alzheimer's_disease:_which_therapeutic_perspectives]_ DB - PRIME DP - Unbound Medicine ER -