TY - JOUR
T1 - Tau proteins in the temporal and frontal cortices in patients with vascular dementia
AU - Mukaetova-Ladinska, Elizabeta B.
AU - Abdel-All, Zeinab
AU - Mugica, Estibaliz Santiago
AU - Li, Mosi
AU - Craggs, Lucy J L
AU - Oakley, Arthur E.
AU - Honer, William G.
AU - Kalaria, Raj N.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
KW - Aging
KW - Alzheimer disease
KW - Ischemia
KW - Microvascular
KW - Stroke
KW - Tau
KW - Vascular dementia.
UR - http://www.scopus.com/inward/record.url?scp=84921902228&partnerID=8YFLogxK
U2 - 10.1097/NEN.0000000000000157
DO - 10.1097/NEN.0000000000000157
M3 - Article
C2 - 25575131
AN - SCOPUS:84921902228
VL - 74
SP - 148
EP - 157
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
SN - 0022-3069
IS - 2
ER -