Elevated plasma levels of the protein clusterin were associated with AD prevalence and severity, but they did not predict AD incidence or distinguish between AD and vascular dementia.

Plasma clusterin has been reported to be associated with baseline severity of Alzheimer disease (AD) and with the speed of AD progression and brain atrophy. Furthermore, the locus of the gene that encodes for this protein has been implicated in AD.

To assess the value of plasma clusterin as an AD biomarker, researchers analyzed data from a randomly selected subcohort of 926 participants in the large, prospective, population-based Rotterdam Study. Each participant had undergone brief cognitive screening with the Mini-Mental State Examination and the Geriatric Mental State Schedule; subsequent neuropsychological testing was conducted in those with an MMSE score <26 or a GMSS organic level above zero.

During a mean follow-up of 7.2 years, 61 of the 926 participants in the subcohort were diagnosed with dementia according to standard criteria. To these 61, the researchers added 178 people from the larger cohort who developed dementia during follow-up and another 77 who had a dementia diagnosis upon study entry. After adjustment for multiple dementia risk factors (e.g., older age, less education, apolipoprotein E 4 carrier status, vascular risk factors), no clear association between incident dementia and plasma clusterin levels was found. Plasma clusterin also did not discriminate effectively between AD and vascular dementia. Elevated plasma clusterin levels were, however, significantly associated with AD diagnosis at the time of study entry (i.e., with AD prevalence) and with greater AD severity.

Comment: The authors acknowledge that, given their data, plasma clusterin is not a useful biomarker for predicting the development of AD. However, the current findings point to a possible neuroprotective role of clusterin in dementia. Harnessing clusterin in AD therapy may warrant exploration.

Source: Journal Watch Neurology