Pathology

Alzheimer's disease is principally characterised by neurofibrillary tangles and senile plaques (1,2).

Neurofibrillary tangles are found on silver staining adjacent to the nucleus, within a cell body.

• They are found particularly in pyramidal cells of the association neocortex, in the hippocampus, and in certain subcortical nuclei which send projections to the cerebral cortex such as the nucleus basalis of Meynert, from which there is an ascending cholinergic projection.
• The tangles contain an abnormally phosphorylated microtubule associated protein tau, which fails to bind to microtubules leading to collapse of the neuronal cytoskeleton.
• The presence of neurofibrillary tangles may predict subsequent neuronal death.

Senile plaques consist of dystrophic axons and dendrites clustered around an amyloid core.

• The amyloid is composed of beta-amyloid (Aβ) protein which is a proteolytic fragment of a larger membrane-spanning protein called beta-amyloid precursor protein.
  • AD pathology is considered with Aβ plaques are observed (2).
• Alternative proteolytic processing of the precursor protein yields peptides which have a high or low tendency to aggregate.

Reference:

• (1) Rossor, M. (1993). Alzheimer’s Disease. BMJ: British Medical Journal, 307(6907), 779–782. http://www.jstor.org/stable/29721161.
• (2) Thal DR, von Arnim C, Griffin WS, Yamaguchi H, Mrak RE, Attems J, Upadhaya AR. Pathology of clinical and preclinical Alzheimer's disease. Eur Arch Psychiatry Clin Neurosci. 2013 Nov;263 Suppl 2:S137-45. doi: 10.1007/s00406-013-0449-5. PMID: 24077890.