Answer
Alzheimer disease (AD) is the most common neurodegenerative disease responsible for dementia. About half of dementia cases result from AD [3, 4] ; however, a variable but measurable amount of AD pathologic changes exist in most cognitively intact elderly individuals who undergo autopsy, indicating that AD is a chronic disease with latent and prodromal stages and suggesting that individuals may have varying abilities to compensate, either biologically or functionally, for the presence of AD. [8]
As with many neurodegenerative diseases, both rare autosomal-dominant forms of AD and more common sporadic forms with genetic risk factors without causative mutations exist. Abnormalities in three genes are known to cause AD with high penetrance: APP, PSEN1, and PSEN2. Autosomal-dominant forms of AD tend to be more severe and occur at a younger age than sporadic AD, but these are relatively rare. Sporadic AD accounts for the vast majority of AD cases. The neuropathologic changes of autosomal-dominant and sporadic AD are largely the same.
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Dementia pathology. Bielschowsky silver staining of the cortex at 400× magnification demonstrates a neurofibrillary tangle (black arrow) and a neuritic plaque (white arrow).
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Dementia pathology. Congo red staining of a small cortical artery at 400× magnification demonstrates salmon-colored amyloid deposition in the media of the vessel.
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Dementia pathology. A: Hematoxylin-eosin-Luxol fast blue staining of the basal ganglia at 100× magnification demonstrates a cavitary infarct. Calcific medial sclerosis of small arteries is also present. B: At 400× magnification, numerous foamy macrophages are present within the center of the infarcted tissue.
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Dementia pathology. A: Hematoxylin and eosin staining of the substantia nigra at 400× magnification demonstrates multiple Lewy bodies within a pigmented neuron. The Lewy bodies are round with a densely eosinophilic core surrounded by a clear halo. B: Immunohistochemical staining (brown) against alpha-synuclein at 400× magnification reveals a round Lewy body within the soma of a neuron.
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Dementia pathology. Comorbid brain pathologies are common in the elderly population. This Venn diagram demonstrates the co-occurrence of brain pathologies as evident from population-based autopsy studies of brain aging.
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Dementia pathology. A: Hematoxylin and eosin staining at 400× magnification of the dentate fascia of the hippocampus reveals round eosinophilic Pick bodies (arrows) in the soma of granular neurons. B: Immunohistochemical staining (brown) against tau at 400× magnification reveals round intraneuronal Pick bodies in cortical neurons.
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Dementia pathology. A: Hematoxylin and eosin staining at 400× magnification of the cerebral cortex reveals the coalescent clear vesicles characteristic of spongiform encephalopathy. B: Immunohistochemical staining (brown) against protease-resistant prion protein reveals the granular immunoreactivity seen in Creutzfeldt-Jakob disease.
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Dementia pathology. Immunohistochemical staining (brown) against tau at 400× magnification reveals glial immunoreactivity that is characteristic of this case of cortico-basal ganglionic degeneration.
