Bridging integrator 1 (BIN1)

Synonyms: amphiphysin 2, AMPH2, AMPHL, SH3P9

Bridging integrator 1 (BIN1) is a widely expressed adaptor protein that is part of the Bin1/amphiphysin/RVS167 (BAR) family. BIN1 functions in clathrin-mediated endocytosis and endocytic recycling, as does the AD risk gene PICALM. Whereas brain-specific isoforms may be involved in the retrieval of synaptic vesicles, ubiquitous isoforms of BIN1 participate in apoptosis, inflammation and calcium homeostasis.

The bulk of the scientific literature on BIN1 concerns its initially identified roles in tumor suppression and muscle development, but in 2010, a large genome-wide association study (GWAS) discovered that BIN1 was a risk factor for late-onset Alzheimer’s disease. This association was confirmed in subsequent GWAS in different populations and in meta-analyses, and BIN1 remains near the top of AlzGene.

The pathogenic mechanism of BIN1 is unknown. A clustering of high-risk polymorphisms upstream of the gene points toward a potential effect on transcription, and AD patients carrying such BIN1 variants have been found to have elevated BIN1 expression in the brain. DNA methylation of the BIN1 promoter has been suggested as a possible epigenetic mechanism influencing AD risk.

BIN1 has also been proposed to modulate tau pathology, but the AD-associated variants known to date do not affect CSF tau levels. As an endocytic accessory protein, BIN1 could potentially affect BACE trafficking and APP metabolism, as well. The BIN1 risk locus has been reported to track with certain brain imaging features of AD.


Alzpedia Citations

  2. BACE1
  3. APP

External Citations

  1. AlzGene

Further Reading


  1. . Bridging integrator 1 (BIN1): form, function, and Alzheimer's disease. Trends Mol Med. 2013 Jul 17; PubMed.
  2. . Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA. 2010 May 12;303(18):1832-40. PubMed.
  3. . Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology. Mol Psychiatry. 2013 Nov;18(11):1225-34. Epub 2013 Feb 12 PubMed.
  4. . Meta-analysis for genome-wide association study identifies multiple variants at the BIN1 locus associated with late-onset Alzheimer's disease. PLoS One. 2011;6(2):e16616. PubMed.
  5. . Genotype patterns at PICALM, CR1, BIN1, CLU, and APOE genes are associated with episodic memory. Neurology. 2012 May 8;78(19):1464-71. PubMed.
  6. . Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE. PLoS Genet. 2011 Feb;7(2):e1001308. PubMed.
  7. . Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease. PLoS One. 2011;6(2):e15918. PubMed.
  8. . BIN1 gene rs744373 polymorphism contributes to Alzheimer's disease in East Asian population. Neurosci Lett. 2013 Jun 7;544:47-51. PubMed.