Is A-beta the foundation for all dementias?
Interesting news summary from the Alzheimer's Research Forum: http://www.alzforum.org/new/detail.asp?id=2544
Common Ground: Is AÎ² the Foundation for Multiple Dementias?
27 August 2010. The majority of patients with Parkinson disease eventually develop dementia, but what pathology underlies this decline? In PD, as well as in dementia with Lewy bodies (DLB), intracellular aggregates composed primarily of Î±-synuclein gum up the specific dopaminergic neurons, but PD patients live with these Lewy bodies for many years before they experience cognitive losses. Intriguingly, scientists have found evidence of amyloid-Î² (AÎ²) pathology in both Parkinson disease dementia (PDD) and DLB, suggesting a role for AÎ² in these diseases. Now, two new papers firm up that idea. In the August 18 Neurology online, researchers led by Andrew Siderowf at the University of Pennsylvania, Philadelphia, report on the first longitudinal study to examine changes in the Alzheimerâs marker AÎ²42 in the cerebrospinal fluid (CSF) of PD patients. They found that low levels of AÎ²42 predicted significant cognitive decline within the next two years, hinting that AÎ² pathology is involved in Parkinsonâs dementia. Meanwhile, in the August 23 Lancet, scientists led by Murat Emre at Istanbul University, Turkey, describe the largest trial to date studying the efficacy of the N-methyl D-aspartate (NMDA) receptor antagonist memantine, which is approved for treatment of AD, in patients with PDD and DLB. Emre and colleagues found that memantine provides a moderate benefit to DLB patients. Together, these studies raise intriguing questions about the interrelatedness of these disorders, with implications for research, diagnosis, and treatment.
The importance of CSF AÎ² as a biomarker has already been demonstrated in AD, with studies showing that in people with mild cognitive impairment, low CSF levels of AÎ² and high levels of tau predict cognitive decline and conversion to AD (see, e.g., Hansson et al., 2006 and Shaw et al., 2009). Low CSF AÎ² levels are thought to reflect the sequestration of AÎ² into amyloid plaques. For PD patients, several cross-sectional studies have shown an association between cognitive impairment and CSF levels of AÎ² and tau as well (see Mollenhauer et al., 2005; Bibl et al., 2006; Compta et al., 2009; Alves et al., 2010), but longitudinal data were missing.
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