Which histologic findings are characteristic of Alzheimer disease?

Updated: Dec 23, 2019
  • Author: Thomas J Montine, MD, PhD; Chief Editor: Adekunle M Adesina, MD, PhD  more...
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AD is characterized diagnostically by two histologic findings: (1) extracellular amorphus eosinophilic deposits of amyloid consisting of Aβ peptides (a cleavage product of amyloid precursor protein [APP]), which are referred to as amyloid plaques, and (2) intraneuronal aggregates of abnormally modified microtubule-associated protein tau (neurofibrillary tangles) (see the image below). [9]

Dementia pathology. Bielschowsky silver staining o Dementia pathology. Bielschowsky silver staining of the cortex at 400× magnification demonstrates a neurofibrillary tangle (black arrow) and a neuritic plaque (white arrow).

Both amyloid plaques and neurofibrillary tangles are readily identified using silver staining techniques such as Bielschowsky or Gallyas. Amyloid plaques are sometimes referred to as “senile plaques” in older literature because of their long association with dementia. Amyloid plaques with evidence of damaged neuronal processes are called neuritic plaques. [10]

Accumulating evidence suggests that Aβ is involved in the etiology of AD, although the mechanism has not been fully elucidated. Amyloid angiopathy is another pathologic finding in the AD spectrum, in which Aβ accumulates in the media of small arteries. Amyloid angiopathy can be identified using stains for amyloidal protein (Congo red, thioflavin-S), or immunohistochemical staining against Aβ (see the image below). Although amyloid angiopathy has been associated with lobar hemorrhages, it is not a strong predictor of cognitive status.

Dementia pathology. Congo red staining of a small Dementia pathology. Congo red staining of a small cortical artery at 400× magnification demonstrates salmon-colored amyloid deposition in the media of the vessel.

Pathologic criteria for the diagnosis of AD require the presence of neuritic plaques [10] ; however, neuritic plaque burden does not correlate well with cognitive status during life. Instead, neurofibrillary tangle distribution is more strongly associated with cognitive status.

The staging criteria for neurofibrillary tangle distribution has six levels (I-VI) referred to as the Braak stage, with each successive stage demonstrating tangles in additional brain regions. [11] Neurofibrillary tangles are present in transentorhinal cortex in stage I, in the CA1 sector of the hippocampus in stage II, in the subiculum in stage III, in other areas of the hippocampus and the entorhinal cortex in stage IV, in the association cortex in stage V, and in the primary motor or sensory cortex or the granule neurons of dentate fascia in stage VI. [11, 12, 13]

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