title: Tau proteins in the temporal and frontal cortices in patients with vascular dementia.
abstract: We previously reported that, in the brains of older patients with vascular dementia (VaD), there is a distinctive accumulation of detergent-extractable soluble amyloid-β, with a predominance of Aβ42 species. It is unclear, however, if tau proteins also accumulate in the brains of older VaD subjects. Using antibody-specific immunoassays, we assessed concentrations of total tau (t-tau) and phosphorylated tau protein, measured at 3 phosphorylated sites (i.e. Thr181, Ser202/Thr205, and Ser262), as well as synaptophysin in the temporal and frontal cortices of 18 VaD, 16 Alzheimer disease (AD), and 16 normal age-matched control subjects. There was selective loss of t-tau protein in VaD compared with controls and AD subjects (p < 0.021 and p < 0.001, respectively). In contrast, phosphorylated tau levels were similar to controls in VaD in both regions, but they were increased in the temporal lobes of patients with AD (p < 0.01 and p < 0.0001 for Ser202/Thr205 and Ser262 phosphorylated sites, respectively). The reduced t-tau in the VaD group was unrelated to any low-level neurofibrillary or amyloid pathology or age at death. These findings suggest that breaches of microvascular or microstructural tissue integrity subsequent to ischemic injury in older age may modify tau protein metabolism or phosphorylation and have effects on the burden of neurofibrillary pathology characteristic of AD.
authors.affiliation: From the Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom (EBM-L, ZA-A, ESM, ML, LJLC, AEO, RNK); and Institute of Mental Health, University of British Columbia, Vancouver, British Columbia, Canada (WGH).
authors.forename: Elizabeta B
authors.initials: EB
authors.lastname: Mukaetova-Ladinska
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Abdel-All
authors.forename: Estibaliz Santiago
authors.initials: ES
authors.lastname: Mugica
authors.forename: Mosi
authors.initials: M
authors.lastname: Li
authors.forename: Lucy J L
authors.initials: LJ
authors.lastname: Craggs
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Oakley
authors.forename: William G
authors.initials: WG
authors.lastname: Honer
authors.forename: Raj N
authors.initials: RN
authors.lastname: Kalaria
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015140:Dementia, Vascular / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D010766:Phosphorylation; D018709:Statistics, Nonparametric; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins