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Alkaline phosphatase has been found on neuronal membranes and plasma alkaline phosphatase (ALP) activity increases during brain injury and cerebrovascular diseases, suggesting that its levels may reflect the neuronal loss. It is known that ALP is higher in subjects affected by Alzheimer's dementia and inversely correlated with cognitive functions. No study has investigated the relationship between ALP and cognitive functions in old-age subject with pre-clinical cognitive impairment. This is a cross-sectional study with data gathered from the ReGAl 2.0 project (Rete Geriatrica Alzheimer-Geriatric Network on Alzheimer's disease), a large Italian multicentric clinical-based study. A cohort of 209 old-age subjects healthy controls (HC), Subjective cognitive decline (SCD), and Mild Cognitive Impairment (MCI) was included in the study. Cognitive performances were assessed with a large neuropsychological battery. The same day, serum alkaline phosphatase activity was measured in all subjects. We found that the SCD group had significantly higher ALP levels as compared with HC (p = 0.001). Among all neuropsychological tests, in all population ALP levels negatively correlated with scores at attentional matrices (r =  - 0.243, p = 0.002), Digit Span Forward (r =  - 0.241, p = 0.003) and Letter Fluency Test (r =  - 0.196, p = 0.044). Attentional Matrices (r =  - 0.208, p = 0.014) and Letter Fluency Test (r =  - 0.229, p = 0.019) remained significantly correlated with ALP even after controlling for gender. In the SCD group, only the Attentional Matrices significantly and negatively correlated with ALP (r =  - 0.344 p = 0.035), while no significant correlations were found in HC or MCI. Results indicate that serum alkaline phosphatase activity is increased in SCD and inversely correlates with cognitive functions. Further studies are needed to investigate the role of ALP in the progression to AD.


Virginia Boccardi, Valentina Bubba, Ilenia Murasecco, Martina Pigliautile, Roberto Monastero, Roberta Cecchetti, Michela Scamosci, Patrizia Bastiani, Patrizia Mecocci, ReGAL 2.0 study group. Serum alkaline phosphatase is elevated and inversely correlated with cognitive functions in subjective cognitive decline: results from the ReGAl 2.0 project. Aging clinical and experimental research. 2021 Mar;33(3):603-609

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PMID: 32363431

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