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.