Alzheimer disease

Handb Clin Neurol. 2017;145:325-337. doi: 10.1016/B978-0-12-802395-2.00023-7.

Abstract

Alzheimer disease neuropathology is characterized by the extracellular accumulation of Aβ peptide and intracellular aggregation of hyperphosphorylated tau. With the progression of the disease, macroscopic atrophy affects the entorhinal area and hippocampus, amygdala, and associative regions of the neocortex. The locus coeruleus is depigmented. The deposition of Aβ is first made of diffuse deposits. Amyloid focal deposits constitute the core of the senile plaque which also comprises a corona of tau-positive neurites. Aβ deposits are found successively in the neocortex, the hippocampus, the striatum, the mesencephalon, and finally the cerebellum together with the pontine nuclei (Thal phases). Tau pathology affects in a stereotyped order some specific nuclei of the brainstem, the entorhinal area, the hippocampus, and the neocortex - first the associative areas and secondarily the primary cortices (Braak stages). Loss of synapses is observed in association with tau and Aβ pathology; neuronal loss occurs in the most affected areas. Granulovacuolar degeneration and perisomatic granules are also linked to Alzheimer disease pathology. The physiopathology of Alzheimer disease remains unknown. Familial cases suggest that Aβ deposition is the initial step, but tau pathology appears early in the course and seems to be better correlated with the symptoms.

Keywords: Alzheimer disease neuropathology; abeta deposit; neurofibrillary tangle; neuronal loss; neuropathological criteria; senile plaque; synaptic loss; tau aggregation.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Central Nervous System / metabolism
  • Central Nervous System / pathology*
  • Humans
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • tau Proteins