Background Alzheimer’s disease is a neurological disease marked by memory loss, cognitive decline, and behavioral abnormalities. The major frequent cause of dementia is AD, with an estimated 50 million or more individuals affected globally, these days. Several conventional susceptibility genes have been found in preliminary research, such as the Amyloid Precursor Protein, Apolipoprotein E (APOE) for late onset AD (LOAD), Presenilin genes 1 and 2 for early onset AD (EOAD). Objective In this review paper we highlight the effect of BIN1 in AD. Method of study A total of 110 articles were retrieved from Google Scholar, PubMed and ScienceDirect using various keywords. After full-text evaluation and applying the literature selection criteria, 98 articles were selected in the review. Only studies published in English, covering the human, animal or in vitro aspects of Alzheimer’s disease are included in this list. Articles that were not written in English, treated other topics, were not examining BIN1 or Alzheimer’s disease, were abstracts from conferences, editorials, letters, short papers with missing data or repeated studies were all excluded. From the initial screening, applying the right criteria resulted in 98 articles being chosen for this review to explore and understand BIN1’s connection to Alzheimer’s disease. Results Research revealed a significant locus of susceptibility for LOAD on the Bridging Integrator 1 (BIN1) that is situated on chromosome 2q14.3 and is identified at the time of the most significant susceptibility gene of LOAD. Neuronal circuits connected synaptically are the medium via which tau disease spread, yet the fundamental mechanisms remain unknown. BIN1—amphiphysin 2 is most common genetic risk factor for late onset AD. In brain illness, the neuronal isoform of BIN1-amphiphysin 2 is downregulated. BIN1, or amphiphysin II, is a Bin/Amphiphysin/Rvs (BAR) domain containing protein that controls membrane curvature and participates in clathrin-dependent endocytosis. Changes in BIN1 expression levels have been shown to impair endocytic flux, likely due to problems with vesicle scission and trafficking. Additionally, preventing endocytosis by blocking dyamin also lowers Tau pathology propagation. The cytoplasmic membrane binding protein BIN1 is involved in subcellular trafficking and endocytosis. Conclusion The most frequent BIN1 variants are found in non-coding regions immediately upstream of the gene, and it is thus likely that their impact is regulatory and not structural. The variants can influence the levels of BIN1 or splicing between isoforms, especially the distribution of isoforms. In AD, there is a significant change in expression of BIN1 isoforms, where there is an upregulation of shorter glial-specific isoforms and a downregulation of longer neuronal isoforms. Such isoform imbalance can interfere with neuronal function and play a role in AD pathogenesis, making it essential to target BIN1 splicing regulation as a therapeutic modality. Graphical abstract

A comprehensive review on novel opportunities for Alzheimer therapy by targeting BIN1

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2025年8月7日

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Trina Saha,
Dipanjan Karati

摘要

Background

Alzheimer’s disease is a neurological disease marked by memory loss, cognitive decline, and behavioral abnormalities. The major frequent cause of dementia is AD, with an estimated 50 million or more individuals affected globally, these days. Several conventional susceptibility genes have been found in preliminary research, such as the Amyloid Precursor Protein, Apolipoprotein E (APOE) for late onset AD (LOAD), Presenilin genes 1 and 2 for early onset AD (EOAD).

Objective

In this review paper we highlight the effect of BIN1 in AD.

Method of study

A total of 110 articles were retrieved from Google Scholar, PubMed and ScienceDirect using various keywords. After full-text evaluation and applying the literature selection criteria, 98 articles were selected in the review. Only studies published in English, covering the human, animal or in vitro aspects of Alzheimer’s disease are included in this list. Articles that were not written in English, treated other topics, were not examining BIN1 or Alzheimer’s disease, were abstracts from conferences, editorials, letters, short papers with missing data or repeated studies were all excluded. From the initial screening, applying the right criteria resulted in 98 articles being chosen for this review to explore and understand BIN1’s connection to Alzheimer’s disease.

Results

Research revealed a significant locus of susceptibility for LOAD on the Bridging Integrator 1 (BIN1) that is situated on chromosome 2q14.3 and is identified at the time of the most significant susceptibility gene of LOAD. Neuronal circuits connected synaptically are the medium via which tau disease spread, yet the fundamental mechanisms remain unknown. BIN1—amphiphysin 2 is most common genetic risk factor for late onset AD. In brain illness, the neuronal isoform of BIN1-amphiphysin 2 is downregulated. BIN1, or amphiphysin II, is a Bin/Amphiphysin/Rvs (BAR) domain containing protein that controls membrane curvature and participates in clathrin-dependent endocytosis. Changes in BIN1 expression levels have been shown to impair endocytic flux, likely due to problems with vesicle scission and trafficking. Additionally, preventing endocytosis by blocking dyamin also lowers Tau pathology propagation. The cytoplasmic membrane binding protein BIN1 is involved in subcellular trafficking and endocytosis.

Conclusion

The most frequent BIN1 variants are found in non-coding regions immediately upstream of the gene, and it is thus likely that their impact is regulatory and not structural. The variants can influence the levels of BIN1 or splicing between isoforms, especially the distribution of isoforms. In AD, there is a significant change in expression of BIN1 isoforms, where there is an upregulation of shorter glial-specific isoforms and a downregulation of longer neuronal isoforms. Such isoform imbalance can interfere with neuronal function and play a role in AD pathogenesis, making it essential to target BIN1 splicing regulation as a therapeutic modality.

Graphical abstract