Chasing genes in Alzheimer's and Parkinson'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 the progressive loss of specific neuronal populations and the 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 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 identified that cause or increase susceptibility to AD and PD. This review discusses the way in which strategies of "gene hunting" have evolved during the last few years and the significance of finding genes such as the presenilins, alpha- 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 a few overlapping interrelated pathways. Their imbricate features point to a spectrum of neurodegeneration (tauopathies, synucleinopathies, amyloidopathies) that need further intense investigation to find the missing links.
Genetic Epidemiology Unit, Department of Clinical Genetics, Erasmus MC, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands. a.bertoliavella@erasmusmc.nl
Aida M
AM
Bertoli-Avella
Ben A
BA
Oostra
Peter
P
Heutink
D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics*; D002874:Chromosome Mapping; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D010300:Parkinson Disease / Q000235:genetics*; D053764:Presenilin-1; D053766:Presenilin-2; D051843:Synucleins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology; D051844:alpha-Synuclein
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein