Apolipoprotein A1, the neglected relative of Apolipoprotein E and its potential role in Alzheimer’s disease

Lipoproteins are multi-molecule assemblies with the primary function of transportation and processing of lipophilic substances within aqueous bodily fluids (blood, cerebrospinal fluid). Nevertheless, they also exert other physiological functions such as immune regulation. In particular, neurons are both sensitive to uncontrolled responses of the immune system and highly dependent on a controlled and sufficient supply of lipids. For this reason, the role of certain lipoproteins and their protein-component (apolipoproteins, Apo’s) in neurological diseases is perceivable. ApoE, for example, is well-accepted as one of the major risk factors for sporadic Alzheimer’s disease with a protective allele variant (ε2) and a risk-causing allele variant (ε4). ApoA1, the major protein component of high-density lipoproteins, is responsible for transportation of excess cholesterol from peripheral tissues to the liver. The protein is synthesized in the liver and intestine but also can enter the brain via the choroid plexus and thereby might have an impact on brain lipid homeostasis. This review focuses on the role of ApoA1 in Alzheimer’s disease and discusses whether its role within this neurodegenerative disorder is specific or represents a general neuroprotective mechanism.