Spinal Fluid Assay Useful for Predicting Dementia in Parkinson's

One part of a much-publicized 3-part Innogenetics assay appears to predict dementia in Parkinson disease. According to an early-release, prospective, cohort study (N = 45) from U Penn, low and declining levels of beta amyloid 1-42 in spinal fluid are associated with cognitive impairment in the disorder. There is no association, however, between dementia and CSF levels of total tau, phosphorylated tau, or any tau-to-beta-amyloid ratios. In fact, adding any tau measurement to the mix actually diminishes the predictive value of the beta-amyloid measure in PD patients.

During the 1-3-year PD study, baseline beta amyloid 1-42 levels of less than 192 pg/mL, which are considered diagnostic for Alzheimer disease, significantly increased the risk of dementia. On the basis of their data, the authors concluded that a PD patient with a low CSF beta-amyloid level would "progress from essentially normal cognition to a level consistent with [PD-associated dementia] within a 2-year period of follow-up." CSF beta-amyloid levels also correlated with apolipoprotein E ε4 carrier status among the small number of PD patients (15) who carried the AD risk factor.

Last week, the full 3-part Innogenetics assay (which measures CSF levels of beta amyloid 1-24, total tau, and phosphorylated tau) was promoted to predict AD in people with mild cognitive impairment (see Alzheimer Assay Deserves Qualified Embrace). In this study, there was a distinctive pattern change as MCI progressed to mild AD and then to advanced disease: CSF beta amyloid levels fell while tau levels rose. The former event appears to be true in PD patients who develop dementia. Lower levels of CSF beta amyloid reflect the underlying amyloid pathology of the dementing aspect of the disease and may be due to the sequestration of beta amyloid into developing amyloid plaques. At least that's the speculation.

The Penn authors concluded that the CSF level of beta amyloid 1-42 "may provide clinically useful prognostic information, particularly if combined with other risk factors for cognitive impairment in PD." Dementia may occur in the disorder in up to 80% of patients.

A Belgian company, Innogenetics was acquired by Solvay Pharmaceuticals in 2008 and is listed on Euronext Brussels (ticker, INNX)

Image of 1886 drawing of PD patient by neurologist Sir William Richard Gowers from Wikimedia Commons.