title: Altered Proteins in the Aging Brain.
abstract: 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.
authors.affiliation: From the Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden (AE, SL, IA); and Department of Pathology, Uppsala University Hospital, Uppsala, Sweden (AE, SL, ML, SNP, IA).
authors.forename: Adila
authors.initials: A
authors.lastname: Elobeid
authors.affiliation: From the Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden (AE, SL, IA); and Department of Pathology, Uppsala University Hospital, Uppsala, Sweden (AE, SL, ML, SNP, IA).
authors.forename: Sylwia
authors.initials: S
authors.lastname: Libard
authors.affiliation: From the Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden (AE, SL, IA); and Department of Pathology, Uppsala University Hospital, Uppsala, Sweden (AE, SL, ML, SNP, IA).
authors.forename: Marina
authors.initials: M
authors.lastname: Leino
authors.affiliation: From the Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden (AE, SL, IA); and Department of Pathology, Uppsala University Hospital, Uppsala, Sweden (AE, SL, ML, SNP, IA).
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Popova
authors.affiliation: From the Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden (AE, SL, IA); and Department of Pathology, Uppsala University Hospital, Uppsala, Sweden (AE, SL, ML, SNP, IA). irina.alafuzoff@ipg.uu.se.
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000401:mortality / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human; D051844:alpha-Synuclein; D016875:tau Proteins
keywords: Aging; Cognition; Hyperphosphorylated-τ; Immunohistochemistry; Transactive response DNA binding protein 43.; α-Synuclein; β-Amyloid