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AD and PD genes account for a small % of DLB and PDD
I understood very little of this abstract. However, I'm posting it for two reasons. One, to demonstrate what amazing genetic analyses are going on. Two, to share the conclusion that "mutations in known dementia and PD genes only explain the disease in a small percentage of DLB and PDD patients. The search for additional genes continues.
I glanced over the full article's Introduction, as that's usually more understandable. There seems to be no agreement on the incidence of DLB and PDD. The research article on Namenda/quality-of-life that I posted earlier today says: "Dementia with Lewy bodies (DLB) and Parkinsonâs disease dementia (PDD) are similar diseases and together account for 15Â20% of the global incidence of dementia." While this article says: "DLB is the second most frequent neurodegenerative dementia with an estimated prevalence up to 30% of all dementias... In contrast, the prevalence of PDD is stated to be only 3.6% of all dementia cases based on studies focusing on dementia. However, up to 30% of all Parkinson disease (PD) patients develop dementia during the course of their disease, increasing the actual prevalence of PDD."
Neurobiology of Aging. 2011 Nov 25. [Epub ahead of print]
DLB and PDD: a role for mutations in dementia and Parkinson disease genes?
Meeus B, Verstraeten A, Crosiers D, Engelborghs S, Van den Broeck M, Mattheijssens M, Peeters K, Corsmit E, Elinck E, Pickut B, Vandenberghe R, Cras P, De Deyn PP, Van Broeckhoven C, Theuns J.
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium; Institute Born-Bunge, University of Antwerp, Antwerpen, Belgium.
Based on the substantial overlap in clinical and pathological characteristics of dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) with Alzheimer disease (AD) and Parkinson disease (PD) we hypothesized that these disorders might share underlying genetic factors.
The contribution of both sequence and copy number variants (CNVs) in known AD and PD genes to the genetic etiology of DLB and PDD however is currently unclear.
Therefore, we performed a gene-based mutation analysis of all major AD and PD genes in 99 DLB and 75 PDD patients, including familial and sporadic forms, from Flanders, Belgium. Also, copy number variants in APP, SNCA, and PARK2 were determined.
In the AD genes we detected proven pathogenic missense mutations in PSEN1 and PSEN2, and 2 novel missense variants in PSEN2 and MAPT. In the PD genes we identified 1 SNCA duplication, the LRRK2 R1441C founder mutation and 4 novel heterozygous missense variants with unknown pathogenicity.
Our results suggest a contribution of established AD and PD genes to the genetic etiology of DLB and PDD though to a limited extent. They do support the hypothesis of a genetic overlap between members of the Lewy body disease spectrum, but additional genes still have to exist.
Copyright Â© 2011 Elsevier Inc. All rights reserved.
PubMed ID#: 22118943