AGING-RELATED TAU ASTROGLIOPATHY IN COGNITIVELY NORMAL SUBJECTS

Abstract

Abnormal tau protein deposit is observed in neurons and glial cells in tauopathies and in brain aging; however its clinical significance is still poorly understood. The introduction of new antibodies in the immunohistochemical analysis has enabled the identification of astroglial lesions in brains of aging individuals with and without the presence of other neuropathological changes. Recently the term aging-related tau astrogliopathy (ARTAG) was proposed to describe the morphological spectrum of astroglial pathology detected by tau immunohistochemistry. Here we analyze the frequency of ARTAG in cognitively normal individuals and compare demographics and neuropathological features between individuals with and without associated ARTAG. A total of 122 brains of cognitively normal individuals were investigated. Tau immunostained sections (PHF-1 antibody) of hippocampus and amygdala were assessed for ARTAG. Cognitively normal subjects were defined as having no cognitive impairment according to the Clinical Dementia Rating scale (CDR=0). Demographic and clinical data were collected through interviews with a next-of-kin. Internationally accepted criteria were used to diagnose and stage the brain tissue pathologies. The mean age at death was 69.6± 11.5 years, 52.5% were female, the mean education was 5.5±4.4 years, and 70% were Caucasians. ARTAG was identified in 29% of the sample. Subjects with ARTAG were older (ARTAG: 76.7 ± 10.2 years; non-ARTAG 66.7±10.8 years; p<0.0001). There was no difference in gender, race, socioeconomic status, cerebrovascular risk factors, and presence of APOE Ɛ4 allele between subjects with and without ARTAG. ARTAG without some degree of NFT was observed in only 11.4%. Neuritic plaque burden, presence of lacunar infarcts, arteriolosclerosis, and Lewy-type pathology were similar between subjects with and without ARTAG. Additionally, subjects with ARTAG frequently showed concomitant argyrophilic grain disease compared to without ARTAG (ARTAG: 68.6%; non-ARTAG: 19.5%; p<0.001). Subjects with ARTAG had lower frequency of irritability (ARTAG: 2.9%; non-ARTAG 17.2%; p=0.02) and disinhibition (ARTAG: 0; non-ARTAG 10.3%; p=0.042) than those without ARTAG according the Neuropsychiatric Inventory. ARTAG was associated with older age and frequently with some degree of concomitant AD-type pathology. These results highlight the importance to understand the role of accumulation of astroglial tau in normal and pathological brain aging.