title: [Alzheimer's disease: lesions and their progression].
abstract: Alzheimer disease appears to be a stereotyped mode of reaction of the central nervous system to various types of aggression such as different mutations involving various proteins, trisomy 21 or repeated head trauma as in dementia pugilistica. Rather than a disease, it appears to be a clinicopathological syndrome due to various causes. Lesions may be considered under 3 headings: neurofibrillary pathology, A beta peptide deposits and loss (neuronal and synaptic). Neurofibrillary pathology includes the neurofibrillary tangle, the crown of the senile plaque and the neuropil threads. All those lesions are characterized by the same ultrastructure--i.e. the accumulation of paired helical filaments--and the same immunohistochemistry: they are labelled by antibodies directed against the tau proteins. The amyloid deposits, present in the core of the senile plaque and in the vascular walls, are made of a 40 to 42 amino-acids long peptide, named A beta, derived from the amyloid precursor protein (APP). Antibodies directed against the A beta peptide also label diffuse deposits that are devoid of the tinctorial affinities and of the biochemical properties of amyloid substances. Those diffuse deposits are insufficient to cause dementia since they may be observed in high density in aged people without intellectual deterioration. Neuronal loss occurs after neurofibrillary pathology. The role of the synaptic pathology remains discussed. Besides tau proteins, A beta peptide and APP, several other proteins may play an important role: apolipoprotein E which could act as a chaperone protein, inducing or facilitating the formation of amyloid, presenilins 1 and 2, mutated in some cases of familial Alzheimer disease, alpha-synuclein which is present in the Lewy bodies found in Parkinson disease and in dementia with Lewy bodies. The A beta deposits are diffusely distributed in the cerebral cortex; the neurofibrillary changes have a hierarchical distribution. The progression of the neurofibrillary pathology in the various cortical areas follow a stereotyped sequence that may help to grade the severity of the disease. Progression may take decades. The relations between aging and Alzheimer disease are still poorly understood. Frequency of Alzheimer type lesions in old people could suggest that they are the inevitable burden of age, but this has been discussed.
authors.affiliation: Laboratoire de Neuropathologie R. Escourolle, Hôpital de La Salpêtrière, Paris.
authors.forename: C
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: M A
authors.initials: MA
authors.lastname: Colle
authors.forename: B
authors.initials: B
authors.lastname: Delatour
authors.forename: J J
authors.initials: JJ
authors.lastname: Hauw
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017354:Point Mutation / Q000235:genetics; D013569:Synapses / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins