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Stroke is the fifth leading cause of death in the U.S., with more than 100,000 deaths annually. There are a multitude of risks associated with stroke, including aging, cardiovascular disease, hypertension, Alzheimer’s disease (AD), and immune suppression. One of the many challenges, which has so far proven to be unsuccessful, is the identification of a cost-effective diagnostic or prognostic biomarker for stroke. Alkaline phosphatase (AP), an enzyme first discovered in the 1920s, has been evaluated as a potential biomarker in many disorders, including many of the co-morbidities associated with stroke. This review will examine the basic biology of AP, and its most common isoenzyme, tissue nonspecific alkaline phosphatase (TNAP), with a specific focus on the central nervous system. It examines the preclinical and clinical evidence which supports a potential role for AP in stroke and suggests potential mechanism(s) of action for AP isoenzymes in stroke. Lastly, the review speculates on the clinical utility of AP isoenzymes as potential blood biomarkers for stroke or as AP-targeted treatments for stroke patients.

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Erik C. Brown, Brandon Lucke-Wold, Justin S. Cetas, Aclan Dogan, Sachin Gupta, Timothy E. Hullar, Timothy L. Smith, Jeremy N. Ciporen, Surgical Parameters for Minimally Invasive Trans–Eustachian Tube CSF Leak Repair: A Cadaveric Study and Literature Review, World Neurosurgery, Volume 122, 2019, Pages e121-e129, ISSN 1878-8750,


Author manuscript; available in PMC 2020 Feb 1. Published in final edited form as: Metab Brain Dis. 2019 Feb; 34(1): 3–19. Published online 2018 Oct 4. doi: 10.1007/s11011-018-0322-3