Molecular Pathogenesis of Frontotemporal Lobar Degeneration

Abstract

olecular genetic research provides a valuable tool to increase our understanding of diseases of the brain, which are otherwise difficult to study because of limited accessibility to the diseased tissue during life. One of the classic methods used in molecular genetics is linkage analysis. This is a technique designed to map disease genes in families by examining transmission of genes based on cosegregation of highly polymorphic genetic markers with disease. These genetic markers are mostly short tandem repeats of 2 to 4 nucleotides that can be genotyped at even spacing throughout the genome. Using a statistical algorithm, chromosome regions can be identified that are shared between patients more often than expected by chance. Shared regions are more likely to contain a disease gene. Findings from a single family can be extrapolated to larger groups of patients by exposing key genes and proteins in the pathologic cascade. Eventually, these insights may lead to development of diagnostic markers or therapeutic strategies.

A Decade of Genetic Counseling in Frontotemporal Dementia Affected Families: Few Counseling Requests and much Familial Opposition to Testing

“…There are at least five genes associated with FTD and its subtypes, and even more when one considers the overlap with Alzheimer disease and motor neuron disease (Van der Zee et al 2008 ). The microtubule associated protein tau gene ( MAPT ) was the first FTD gene identified in 1998 (Sleegers et al 2008 ), followed by the progranulin gene ( GRN ) in 2006. The MAPT and GRN mutations are variably found in some 10–20% of familial FTD series (Rademakers et al 2007 ; Rademakers et al 2008 ).…”

Dementia with Parkinson's disease: Clinical diagnosis, neuropsychological aspects and treatment

“…The frontotemporal dementias are linked to genes that regulate the tau protein, known generically as tauopathies, and also with the genes that regulate the TDP-43 protein, among them the progranulin gene. 2 …”