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Neuropathology of Alzheimer's disease: a critical update.

Abstract

The unequivocal diagnosis of Alzheimer's disease (AD) rests on histopathological evidence at brain autopsy or biopsy. The morphology of AD includes cerebral atrophy, deposition of beta A4 amyloid (A beta) (senile plaques and amyloid angiopathy), neuritic changes (neuritic plaques, neurofibrillary tangles (NFT) and neuropil threads) with formation of paired helical filaments (PHF) containing polymerized hyperphosphorylated tau protein triplet, causing disruption of the neuronal cytoskeleton with loss of synapses and neurons, with altered cortico-cortical connectivity, leading to disconnection of the cerebral cortex. Defining criteria for the morphologic diagnosis of AD is difficult due to the phenotypic heterogeneity of the disease, the absence of specific markers, and overlap of AD morphology with that observed in non-demented elderly individuals. This gray zone between normal to pathologic aging and full-fledged AD represents an important diagnostic problem and should be overcome by better standardized criteria that will allow to minimize interrater and interlaboratory variability in the diagnosis of AD. Current criteria for the morphologic diagnosis of AD are based on (semi)quantitative assessment of diffuse and neuritic plaques (NIA), exclusively neuritic plaques (CERAD), plaques and NFT in neocortex and hippocampus (Tierney et al., 1988), and staging of hierarchic spreading of neuritic AD changes (Braak and Braak, 1991); all of them have weaknesses and need to be revalidated. Multivariant analysis of an autopsy series of elderly subjects revealed significant correlations between psychostatus and both the CERAD criteria and Braak staging. Recent recommendations of the NIA-Reagan Institute for the morphologic diagnosis of AD are presented. Although the role of plaques and NFT in the pathogenesis of AD remains undetermined, clinicopathological correlative studies have shown that both lesions, if present in sufficient numbers, particularly in the neocortex, are considered the best morphological signposts for AD. Recent studies on neuron death in AD that, at least in part, appears different from classical apoptosis and may precede the symptomatic stage of AD, have shown varying results indicating only indirect relationship between DNA fragmentation and both A beta deposition and NFTs. Both these AD-typical markers appear to increase the risk of cells to degenerate, but are not the sole responsibles of the degenerative process in AD, the basic mechanisms of which remain to be elucidated.

Authors+Show Affiliations

,

L. Boltzmann Institute of Clinical Neurobiology, Vienna, Austria.

Source

MeSH

Aged
Alzheimer Disease
Amyloid beta-Peptides
Brain
Cytoskeleton
Dementia
Diagnosis, Differential
Humans
Neurofibrillary Tangles
Plaque, Amyloid

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

9850917

Citation

Jellinger, K A., and C Bancher. "Neuropathology of Alzheimer's Disease: a Critical Update." Journal of Neural Transmission. Supplementum, vol. 54, 1998, pp. 77-95.
Jellinger KA, Bancher C. Neuropathology of Alzheimer's disease: a critical update. J Neural Transm Suppl. 1998;54:77-95.
Jellinger, K. A., & Bancher, C. (1998). Neuropathology of Alzheimer's disease: a critical update. Journal of Neural Transmission. Supplementum, 54, pp. 77-95.
Jellinger KA, Bancher C. Neuropathology of Alzheimer's Disease: a Critical Update. J Neural Transm Suppl. 1998;54:77-95. PubMed PMID: 9850917.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropathology of Alzheimer's disease: a critical update. AU - Jellinger,K A, AU - Bancher,C, PY - 1998/12/16/pubmed PY - 1998/12/16/medline PY - 1998/12/16/entrez SP - 77 EP - 95 JF - Journal of neural transmission. Supplementum JO - J. Neural Transm. Suppl. VL - 54 N2 - The unequivocal diagnosis of Alzheimer's disease (AD) rests on histopathological evidence at brain autopsy or biopsy. The morphology of AD includes cerebral atrophy, deposition of beta A4 amyloid (A beta) (senile plaques and amyloid angiopathy), neuritic changes (neuritic plaques, neurofibrillary tangles (NFT) and neuropil threads) with formation of paired helical filaments (PHF) containing polymerized hyperphosphorylated tau protein triplet, causing disruption of the neuronal cytoskeleton with loss of synapses and neurons, with altered cortico-cortical connectivity, leading to disconnection of the cerebral cortex. Defining criteria for the morphologic diagnosis of AD is difficult due to the phenotypic heterogeneity of the disease, the absence of specific markers, and overlap of AD morphology with that observed in non-demented elderly individuals. This gray zone between normal to pathologic aging and full-fledged AD represents an important diagnostic problem and should be overcome by better standardized criteria that will allow to minimize interrater and interlaboratory variability in the diagnosis of AD. Current criteria for the morphologic diagnosis of AD are based on (semi)quantitative assessment of diffuse and neuritic plaques (NIA), exclusively neuritic plaques (CERAD), plaques and NFT in neocortex and hippocampus (Tierney et al., 1988), and staging of hierarchic spreading of neuritic AD changes (Braak and Braak, 1991); all of them have weaknesses and need to be revalidated. Multivariant analysis of an autopsy series of elderly subjects revealed significant correlations between psychostatus and both the CERAD criteria and Braak staging. Recent recommendations of the NIA-Reagan Institute for the morphologic diagnosis of AD are presented. Although the role of plaques and NFT in the pathogenesis of AD remains undetermined, clinicopathological correlative studies have shown that both lesions, if present in sufficient numbers, particularly in the neocortex, are considered the best morphological signposts for AD. Recent studies on neuron death in AD that, at least in part, appears different from classical apoptosis and may precede the symptomatic stage of AD, have shown varying results indicating only indirect relationship between DNA fragmentation and both A beta deposition and NFTs. Both these AD-typical markers appear to increase the risk of cells to degenerate, but are not the sole responsibles of the degenerative process in AD, the basic mechanisms of which remain to be elucidated. SN - 0303-6995 UR - https://www.unboundmedicine.com/medline/citation/9850917/Neuropathology_of_Alzheimer's_disease:_a_critical_update_ L2 - https://medlineplus.gov/alzheimersdisease.html DB - PRIME DP - Unbound Medicine ER -