Whole Exome Sequencing in Alzheimer’s Disease and Frontotemporal Lobar Degeneration

Dementia is a disorder characterized by cognitive impairment and/or behavioral changes that interfere with ability of daily functioning, with Alzheimer’s disease (AD) as the most common form of dementia, and frontotemporal dementia (FTD) as the second most common before age of 65.
My thesis focuses on the genetics of these two types of dementia. Using whole exome sequencing (WES), we have attempted to identify the underlying genetics defects in patients with AD and FTD. WES is a technique that investigates genetic information in protein coding regions of DNA.
We have identified several mutations in two known AD causing genes (PSEN1 and PSEN2) and a potential new risk factor in EIF2AK3 gene in a few patients with AD. In a subset of FTD patients, we have identified the underlying mutations in VCP and TUBA4A genes. At last, using WES and proteomics we have identified a new mutation in PRKAR1B gene in a rare type of dementia with parkinsonian symptoms.
The identification of new genetic defects give us insights in the disease mechanisms involved in AD and FTD. This is important for the development of medication for dementia in the future.