FAM26C polymorphisms and uses thereof for the diagnosis and treatment of late-onset Alzheimer’s disease

Description: Alzheimer’s disease is a progressive neurodegenerative disorder characterized by cerebral amyloid peptide deposition and dementia.  More than 95% of all Alzheimer’s disease cases are late onset, whose symptoms manifest after the age of 65.  To date, the only known susceptibility gene unambiguously linked with late onset Alzheimer’s disease (apolipoprotein E) explains only a tine fraction of the overall heritability of the disease.  In an elegant screen to locate other late onset Alzheimer’s disease susceptibility genes, Drs. Marambaud (Feinstein) and Campagne (Weill Cornell*) recently identified CALHM1, a gene of unknown function, as an additional Alzheimer’s disease risk factor.

Subsequent characterization of CALHM1 revealed that it has amino acid sequence similarity with the selectivity filter of the NMDA receptor and generates a large Ca2+ conductance across the plasma membrane.  Significantly, the frequency of a rare CALHM1 mutation – which results in a single amino acid substitution, loss of Ca2+ permeability control, and increased amyloid peptide deposition – is markedly increased in patients with Alzheimer’s disease.  These results suggest that CALHM1 is a component of a previously uncharacterized cerebral Ca2+ channel involved in amyloid metabolism.

These studies, therefore, suggest that CALHM1 is a pore component of a previously uncharacterized ion channel family and that variants in the CALHM genes may constitute robust risk factors for late onset Alzheimer’s disease.  Given its cell-surface ion channel properties and its restricted expression, this work establishes CALHM1 as a potentially important molecular target for anti-amyloid therapy in Alzheimer’s disease.

Area of Application: Alzheimer’s disease – diagnosis and treatment
Other diseases caused by impaired calcium transport – diagnosis and treatment

Lead Investigator: Philippe Marambaud, PhD

Patent Info: US Patent No. 8,420,309, Issued April 16, 2013*

WIPO Publication No.: WO2009/023145, Publication Date: 2/19/2009

*Feinstein exclusively controls the commercialization right of both Feinstein and Weill Cornell

Reference: Dreses-Werringloer, U. et al., (2008) A polymorphism in CALHM1 influences Ca homeostasis, Aβ levels, and Alzheimer’s disease risk. Cell 133:1149-1161

Licensing Contact:
Kirk R. Manogue, PhD
Director, Office of Technology Transfer
Email: kmanogue@northwell.edu

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