Apoliprotein E (APOE) ε4 is the major genetic risk factor for sporadic Alzheimer’s disease (AD) [1,2]. The risk for developing AD and the age of onset decreases with the number of APOE ε4 alleles [1,2]. The mechanism for this APOE effect is unknown, but is suggested to be linked to aggregation or clearance of amyloid beta (Aβ) [3]. Alzheimer fragments of Aβ1-42 were found to induce fibrillogenesis and be pathogenic [4,5]. These fragments include Aβ17–21, Aβ25–29, Aβ29–33, Aβ33–37, Aβ25–37, Aβ25-35, and Aβ22-40. A motif called the glycine zipper stretch within these fragments was found to be critical in the pathogenesis of AD [4,5]. Nevertheless, only Aβ1-40, Aβ1-42 and Aβ1-38 are quantified in human CSF and remain a trusted class of CSF biomarkers [6]. In an attempt to elucidate the mechanism by which APOE clears Aβ, we monitored the effect on the aggregation of Aβ1-42 (Aβ42) in the presence of Cerebrospinal Fluid (CSF) from healthy and AD patients with different numbers of APOE ε4 alleles [7]. We found that Aβ42 aggregation was delayed in the presence of CSF from healthy controls and AD patients. The effect was significantly enhanced for AD patients with at least one APOE ε4 allele. No significant difference relative to controls was seen for AD patients with no APOE ε4 allele. The same finding was observed in the two independent sample sets. Data suggests that there was at least one substance in CSF that contributed to slowing down the aggregation of Aβ42 into fibrils. This complex was High Density Lipoproteins (HDLs) in CSF, which functioned in tandem with the APOE ε4 allele to slow down the kinetics of Aβ aggregation

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Citation: Padayachee E, Blennow K, Zetterberg H, Portelius E, Borén J, et al (2015) High Density Lipoproteins-Natures Endogenous “Nanovehicles” Are Pushing Alzheimer’s Drug Discovery to New Frontiers. Cell Dev Biol 4:e133 doi:10.4172/2168-9296.1000e133

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