engleski

Acetylation of tau protein at Lys274 in argyrophilic grain disease and Alzheimer’s disease

Argyrophilic grain disease (AGD) is a common sporadic 4R tauopathy. The term ‘argyrophilic grains’ is derived from their strong staining with the Gallyas silver iodide method, although not all silver methods permit their visualization. In combination with Alzheimer’s disease (AD) or alone, AGD significantly contributes to dementia in older age subjects and alone accounts for about 5% of all dementia cases. By using a novel monoclonal antibody specifically immunoreactive to acetylated tau at Lys274 (MAb 359), it has been shown that acetylation of tau protein is an early change in AD brains, which occurs even before tangles are detectable. Interestingly, AGD differs from AD and other tauopathies by lacking tau acetylation at Lys274. By using MAb 359 developed to detect acetylation at Lys274 (a gift from Dr. Li Gan, Gladstone Institute of Neurological Disease, UCSF) we compared immunohistochemically temporal and entorhinal cortex and the hippocampal formation in an AD brain, a brain with pathological changes of AD and AGD, and a brain with AGD alone. Our detailed analysis confirms and expands previous findings and supports further investigations of tau acetylation as a potential new therapeutic target in AD, AGD, and other tauopathies.

Argyrophilic grain disease ; Alzheimer’s disease ; tau acetylation

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