Prof. dr. J.C. van Swieten
Identification of molecular and genetic mechanisms in familial Lewy Body Dementia: a novel approach
Alzheimer's disease & other dementias
Dementia with Lewy Bodies (DLB) is the second most common dementia after Alzheimers Disease in the elderly. Recognizing DLB remains challenging due to the highly variable clinical presentation (varying from cognitive fluctuations, parkinsonism, hallucinations, to sleep disorders) and considerable overlap with AD and Parkinsons Disease (PD). The early diagnosis is further hampered by the lack of cerebrospinal fluid (CSF) and genetic biomarkers. As a consequence, DLB is diagnosed on average 3 years after symptom-onset, a year later than AD. Differentiation from other dementias is clinically relevant, because of a high sensitivity for cholinesterase inhibitor therapy and to avoid the detrimental effects of antipsychotics in DLB.
Aggregation of dementia and PD in families with DLB suggests that genetic susceptibility plays an important role. However, the genetic and molecular mechanisms are still poorly understood.
Whole exome sequencing (WES) is a novel genetic technique used to selectively sequence the coding regions of the genome, which has proven successful in identifying functional variation in small families and in genetical and phenotypical heterogeneous disorders.
Main objective: to identify novel biomarkers to improve the early diagnosis of DLB.
1. to identify proteins that potentially serve as novel biomarker in DLB using brain tissue (Lewy bodies) and cerebrospinal fluid proteomics in patients with familial and pathological proven DLB.
2. to identify novel genetic factors in familial DLB using whole exome sequencing in several families with (pathological proven) DLB.