NIH grant: Lysosomal dysfunction as a risk factor in Alzheimer disease (1R21AG098225-01)

retained text

NIH grant 1R21AG098225-01: Lysosomal dysfunction as a risk factor in Alzheimer disease
Institute: {'code': 'AG', 'abbreviation': 'NIA', 'name': 'National Institute on Aging', 'admin_org_id': '12500002', 'admin_funding_url': ''}. PI: Ernesto Roque Bongarzone. Award: $240495.
Start: 2026-09-25T00:00:00.
SUMMARY
 It is becoming increasingly apparent that lysosomal dysfunction plays a critical role in the development
of diseases like Alzheimer disease (AD), contributing to the accumulation insoluble b-amyloid (Ab) material
and neuronal dysfunction. Various lysosomal enzymes have been recently identified as potentially involved in
disease progression in a large human genomic analysis. We have preliminary data in strong support of this
association indicating that one of these enzymes, galactosyl-ceramidase (GALC) is important for the
accumulation of amyloid material in a mouse model of AD. Biochemical and histological data show that a
reduction in GALC activity by fifty percent of the normal level is associated with almost doubling accumulation
of amyloid material in the brain of the AD mouse. Together, these findings provide the framework for our
working hypothesis that low activity of GALC (and likely, of other lysosomal enzymes) contributes to
neurodegeneration in vulnerable AD patients exacerbating Ab toxicity. To test the feasibility of this theory, this
pilot application will perform biochemical and genomic analyses in a large cohort of AD human cases pre-
screened for changes in GALC expression and in an animal model of AD with partial reduction of GALC activity
to determine the mechanism of this association.

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