Chasing Genes in Alzheimers's and Parkinsons's Disease

Alzheimer’s disease (AD), the most common type of dementia and Parkinson’s disease (PD), the most common movement disorder are both neurodegenerative adult-onset diseases characterized by progressive loss of specifi c neuronal populations and accumulation of intraneuronal inclusions. The search for genetic and environmental factors that determine the fate of neurons during the ageing process has been a widespread approach in the battle against neurodegenerative disorders. Genetic studies of AD and PD have initially focused on the search for genes involved in the aetiological mechanisms of monogenic forms of these diseases. They later expanded to study hundreds of patients, affected relative-pairs and population-based studies sometimes performed on “special” isolated populations. A growing number of genes (and pathogenic mutations) is being identifi ed that cause or increase the susceptibility to AD and PD. This review discussed the way in which strategies of “gene hunting” have evolved during the last years and the signifi cance of fi nding genes such as the presenilins, α-synuclein, parkin and DJ-1. In addition we discuss possible links between these two neurodegenerative disorders. The clinical, pathological and genetic presentation of AD and PD suggests the involvement of few overlapping, interrelated pathways. Their imbricate features point to a spectrum of neurodegeneration (tauopathies, synucleinopathies, amyloidopathies) that will need further intense investigation to find the missing links.

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