Tuesday, April 23, 2024
4/23/2024
PROJECT SUMMARY/ABSTRACT Down syndrome (DS) is the most common chromosomal disorder with an occurrence of 1 in 700 births. It is, by far, the leading known cause of intellectual disability. The longevity of DS people has thankfully increased and several health issues have subsequently emerged, sharing commonality with Alzheimer’s disease (AD). DS is caused by an additional chromosome to the normal 21st pair (Trisomy 21). Chromosome 21 encodes several genes contributing to AD, including proteins that phosphorylate tau, which causes tauopathy in the brain and eye. Multiple ocular anomalies, including cataracts, occur at a much higher frequency starting at younger ages for people with DS. These ocular disorders are associated with A¿ and also tau. To carefully understand the contribution and role of tau in the eye, we adapt a technology platform for the discovery of a panel of nanobodies (Nbs) for A¿ in our parent grant that can be used as specific probes to investigate the histological distribution of tau in the eye (retina and lens tissue). These Nbs would allow us to identify overlooked and potentially rare tau forms and their localization in DS eyes, perhaps yielding also some important insights for AD. For this supplement, our specific aims mirror those of our parent grant for tau: (1) Discover, produce, and validate Nbs against different conformations of tau forms and (2) Test and validate our panel of Nbs using eye tissues and lens from AD mouse models recapitulating DS.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
