Review:The Genetic Epidemiology of Neurodegenerative Disease

The article reviewed here is ‘The Genetic Epidemiology of Neurodegenerative Disease’ by Bartram and Tanzi and freely available here. This is a shortish review article without stated methodology which covers some of the main neurodegenerative disease – Alzheimer’s Disease, Parkinson’s Disease, Lewy Body Dementia, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Huntington Disease and Prion Disease. In the introduction, the authors cover issues including the hypothesis that common gene variants CNV’s contribute significantly to common diseases. They also look at the difficulties associated with interpreting small genetics studies

‘Additional, and commonly cited, problems in finding complex disease genes beyond the most obvious are multiple testing, publication bias, and questionable replication‘

and further that

‘In the case of multiple conflicting reports, metaanalysis across all published studies and/or the evidence for a biochemical/functional consequence of the putative risk allele can help distinguish real disease genes from their harmless counterparts‘

Firstly the authors look at Alzheimer’s Disease (AD) and note the contrast between the genetics of early and late-onset Alzheimer’s Disease. The article covers the well documented associations with early onset AD and also the ApoE4 association with late-onset AD. As this is a 2005 article they will not have been aware of the more recent findings regarding the CLU, PICALM and CR1 genes although the other findings are just as valid today as when the article was first written and the authors provide a concise overview. In the second section on Parkinson’s Disease, the authors contrast the relative success in identifying genes in the early-onset form of Parkinson’s Disease (Parkin genes and Alpha-Synuclein genes) with that in late-onset Parkinson’s Disease.

In the next section they focus on LBD and look at alpha-synuclein, while in the section on Frontotemporal Dementia they focus prominently on the established link with Microtubule Associated Protein Tau. In the section on Amyotrophic Lateral Sclerosis they look at the associations with MAPT (as in FTD), Superoxide Dismutase 1 and ALS2. When considering Huntington’s Disease, they note the importance of the Huntingtin gene as well as a number of gene associations which are thought to influence the onset of the disease. In the section on Prion diseases they look at the PRN gene and the ramifications of various mutations of this gene. While this is four years old, it gives a useful overview of gene studies in the neurodegenerative diseases which can be supplemented by more recent reviews in the area(s) of interest.

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