Biomarkers

Area of Science:

• Neuroscience
• Genetics
• Radiology

Background:

• The PSEN1 A431E mutation, prevalent in Mexico, is linked to spastic paraparesis in Alzheimer's disease (AD).
• The exact cause of spastic paraparesis in this AD subtype is not fully understood.
• This study investigates neurofibrillary tangle deposition patterns in A431E mutation carriers.

Purpose of the Study:

• To characterize neurofibrillary tangle (NFT) deposition in individuals with the PSEN1 A431E mutation.
• To explore the relationship between NFT deposition and spastic paraparesis in this AD subtype.
• To compare NFT patterns between A431E mutation carriers and other AD groups.

Main Methods:

• Flortaucipir PET (FTP) scans and clinical evaluations were performed on 16 symptomatic A431E mutation carriers.
• A comparison group included 20 individuals with non-spastic ADAD mutations or sporadic AD.
• Standardized uptake value ratios (SUVRs) were calculated and compared between groups using t-tests.

Main Results:

• A431E carriers showed significantly elevated FTP in widespread brain areas compared to controls.
• NFT deposition was most pronounced in the para-, pre-, and post-central gyri in the A431E group.
• Entorhinal cortex FTP SUVRs were non-significantly higher in the A431E cohort.

Conclusions:

• The PSEN1 A431E mutation is associated with more severe neurofibrillary tangle pathology than other AD forms, even when matched for disease severity.
• NFT deposition is particularly prominent in the peri-Rolandic cortex in A431E mutation carriers.
• This enhanced pathology likely contributes to the spastic paraparesis observed in this specific AD subtype.