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Open AccessReview

Flotillin: A Promising Biomarker for Alzheimer’s Disease

1
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
2
Neuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash sUniversity Malaysia, Bandar Sunway 47500, Selangor, Malaysia
*
Authors to whom correspondence should be addressed.
J. Pers. Med. 2020, 10(2), 20; https://doi.org/10.3390/jpm10020020 (registering DOI)
Received: 6 March 2020 / Revised: 19 March 2020 / Accepted: 20 March 2020 / Published: 26 March 2020
(This article belongs to the Special Issue Novel Biomarkers in Alzheimer’s Disease)
Alzheimer’s disease (AD) is characterized by the accumulation of beta amyloid (Aβ) in extracellular senile plaques and intracellular neurofibrillary tangles (NFTs) mainly consisting of tau protein. Although the exact etiology of the disease remains elusive, accumulating evidence highlights the key role of lipid rafts, as well as the endocytic pathways in amyloidogenic amyloid precursor protein (APP) processing and AD pathogenesis. The combination of reduced Aβ42 levels and increased phosphorylated tau protein levels in the cerebrospinal fluid (CSF) is the most well established biomarker, along with Pittsburgh compound B and positron emission tomography (PiB-PET) for amyloid imaging. However, their invasive nature, the cost, and their availability often limit their use. In this context, an easily detectable marker for AD diagnosis even at preclinical stages is highly needed. Flotillins, being hydrophobic proteins located in lipid rafts of intra- and extracellular vesicles, are mainly involved in signal transduction and membrane–protein interactions. Accumulating evidence highlights the emerging implication of flotillins in AD pathogenesis, by affecting APP endocytosis and processing, Ca2+ homeostasis, mitochondrial dysfunction, neuronal apoptosis, Aβ-induced neurotoxicity, and prion-like spreading of Aβ. Importantly, there is also clinical evidence supporting their potential use as biomarker candidates for AD, due to reduced serum and CSF levels that correlate with amyloid burden in AD patients compared with controls. This review focuses on the emerging preclinical and clinical evidence on the role of flotillins in AD pathogenesis, further addressing their potential usage as disease biomarkers.
Keywords: flotillin; Alzheimer’s disease; biomarker; exosomes; beta-amyloid; Tau flotillin; Alzheimer’s disease; biomarker; exosomes; beta-amyloid; Tau
MDPI and ACS Style

Angelopoulou, E.; Paudel, Y.N.; Shaikh, M.F.; Piperi, C. Flotillin: A Promising Biomarker for Alzheimer’s Disease. J. Pers. Med. 2020, 10, 20.

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