This major study of whole-genome sequencing in progressive supranuclear palsy (PSP) was published last week (January 30, 2024) online by the NIH. Researchers analyzed brain tissue from 1,441 people with autopsy-confirmed PSP. As hundreds of these cases came from those who donated to the Mayo Clinic in Jacksonville, we at Brain Support Network are proud of our role in this important new study! And we thank all the donors and families who made this research possible.

Here’s a link to the study’s abstract.

And the full pre-print is available for free online. (As a “pre-print,” this study has not yet been peer-reviewed by a journal.)

There have been ten genome-wide association studies (GWAS) to date. As this new major study notes:

Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs).

In this latest study, whole genome sequencing (WGS) was performed. Researchers confirmed six previously-known risk loci (including MAPT, also called the tau gene); these had been found in the GWAS. Associated with those six previously-known genes linked to PSP, the WGS uncovered some rare variants. Additionally, researchers found six new risk loci (incuding APOE).

APOE is very interesting because this has been widely-studied in Alzheimer’s disease (AD).  APOE2 confers a protective role in AD. The researchers state:

Notably, in contrast to Alzheimer’s disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP.

According to an excellent overview of this study, published yesterday (February 8, 2024) on Alzforum:

MAPT was the strongest risk gene for PSP in this and previous studies. … Most striking was the direction of APOE’s relationship to PSP: APOE2 seemed to make it go up. People with PSP were four times as likely to carry two copies of APOE2 than controls. APOE2 carriers with PSP also had more tau pathology postmortem than did PSP cases with other APOE alleles.

David Holtzman of Washington University comments about APOE2 and APOE4 on Alzforum. In short, he says: “I don’t think we can say from this genetic analysis that it means that with PSP, E2 increases and E4 decreases tauopathy.”

Though this research is hard-to-understand, we laypeople can certainly get the gist of it. We know that progress is being made. And we can thank brain donors for their important contributions!

If you are interested in making brain donation arrangements for yourself or your family member, please contact our team at Brain Support Network. And learn more about brain donation from our website.

Robin