Altered Proteins in the Aging Brain

• Published in: Journal of neuropathology and experimental neurology Vol. 75; no. 4; pp. 316 - 325
• Main Authors: Elobeid, Adila, Libard, Sylwia, Leino, Marina, Popova, Svetlana N., Alafuzoff, Irina
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-04-2016; by American Association of Neuropathologists, Inc
• Subjects: Age Factors; Aged; Aged, 80 and over; Aging - pathology; alpha-Synuclein - genetics; alpha-Synuclein - metabolism; Alzheimer Disease - mortality; Alzheimer Disease - pathology; Amyloid beta-Peptides - metabolism; Brain - metabolism; Brain - pathology; DNA-Binding Proteins - metabolism; Female; Humans; Longitudinal Studies; Male; Middle Aged; Original; Pathology; Patologi; Phosphorylation; tau Proteins - metabolism; Tauopathies - metabolism; Tauopathies - pathology; Immunohistochemistry; α-Synuclein; Transactive response DNA binding protein 43; β-Amyloid; Aging; Cognition; Hyperphosphorylated-τ; beta-Amyloid; Hyperphosphorylated-tau; alpha-Synuclein
• ISSN: 0022-3069; 1554-6578; 1554-6578
• DOI: 10.1093/jnen/nlw002

We assessed the prevalence of common altered brain proteins in 296 cognitively unimpaired subjects ranging from age 50 to 102 years. The incidence and the stage of hyperphosphorylated-τ (HPτ), β-amyloid, α-synuclein (αS), and transactive response DNA (TDP) binding protein 43 (TDP43)-immunoreactivity (-IR) increased with age. HPτ-IR was observed in 98% of the subjects; the locus coeruleus was solely affected in 46%, and 79% of the subjects were in Braak stages a to II. β-Amyloid was seen in 47% of subjects and the Thal phase correlated with the HPτ Braak stage and age. Intermediate Alzheimer disease-related pathology (ADRP) was seen in 12%; 52% of the subjects with HPτ-IR fulfilled criteria for definite primary age-related tauopathy (PART). The incidence of concomitant pathology (αS, TDP43) did not differ between those with PART and those with ADRP but the former were younger. TDP43-IR was observed in 36%; the most frequently affected region was the medulla; αS-IR was observed in 19% of subjects. In 41% of the subjects from 80 to 89 years at death, 3 altered proteins were seen in the brain. Thus, altered proteins are common in the brains of cognitively unimpaired aged subjects; this should be considered while developing diagnostic biomarkers, particularly for identifying subjects at early stages of neurodegenerative diseases.