BIN1 localization is distinct from Tau tangles in Alzheimer's disease.

Abstract

BIN1 is the second most significant Alzheimer's disease (AD) risk factor gene identified through genome-wide association studies. BIN1 is an adaptor protein that can bind to several proteins including c-Myc, clathrin, adaptor protein-2 and dynamin. BIN1 is widely expressed in the brain and peripheral tissue as ubiquitous and tissue-specific alternatively spliced isoforms that regulate membrane dynamics and endocytosis in multiple cell types. The function of BIN1 in the brain and the mechanism(s) by which AD-associated BIN1 alleles increase the risk for the disease are not known. BIN1 has been shown to interact with Tau and two studies reported a positive correlation between BIN1 expression and neurofibrillary tangle pathology in AD. However, an inverse correlation between BIN1 expression and Tau propagation has also been reported. Moreover, there have been conflicting reports on whether BIN1 is present in tangles. A recent study characterized predominant BIN1 expression in mature oligodendrocytes in the gray matter and the white matter in rodent, and the human brain. Here, we have examined BIN1 localization in the brains of patients with AD using immunohistochemistry and immunofluorescence techniques to analyze BIN1 cellular expression in relation to cellular markers and pathological lesions in AD. We report that BIN1 immunoreactivity in human AD is not associated with neurofibrillary tangles or senile plaques. Moreover, our results show that BIN1 is not expressed by resting and activated microglia, astrocytes, or macrophages in human AD. In accordance with a recent report, low-level de novo BIN1 expression can be observed in a subset of neurons in the AD brain. Further investigations are warranted to understand the complex cellular mechanisms underlying the observed correlation between BIN1 expression and the severity of tangle pathology in AD.