Anatomic Pathology: Neuropathology

• Protein aggregation is a common finding in neurodegenerative diseases and can help classified diseases according to the protein that accumulates in different groups,such as Alzheimer disease, prion disease, tauopathies, and α-synucleoplathies. Aggregation of proteins can be the result of protein misfolding, in the case of tau accompanied by hyperphosphorylation.

• In Alzheimer disease, β Amyloid deposits form extracellular aggregates called amyloid plaques.

• Tauopathies, such as progressive supranuclear palsy, corticobasal degeneration, and frontotemporal lobe dementia, share with Alzheimer disease the presence of cytoplasmic, fibrillar aggregates of tau protein termed neurofibrillary tangles.

• In Pick disease, a tauopathy, basophilic, round and well-demarcated cytoplasmic inclusions are seen and are called Pick bodies. These inclusions also stain with the antitau antibodies that react with neurofibrillary tangles.

• Parkinson disease (PD) and dementia with Lewy bodies reveal cytoplasmic accumulations of α-synuclein called Lewy bodies. In multiple system atrophy, cytoplasmic inclusions positive for α-synuclein are seen predominantly in oligodendrocytes and are called glial cytoplasmic inclusions.

• In prion diseases, misfolded and aggregated versions of the normal cellular prion protein (PrP) are identified.