Searching the Linkage between High Fat Diet and Alzheimer′s Disease: A Debatable Proof Stand for Ketogenic Diet to Alleviate Symptoms of Alzheimer′s Patient with APOE ε4 Allele

Abstract

Alzheimer’s disease (AD) is an incurable neurodegenerative form of dementia affecting millions of individuals worldwide. A hallmark of AD is the deregulation of the level of s-amyloid (As) that leads to the appearance of the senile plaques that contain As derived from the cleavage of the amyloid precursor protein. Among numerous risk factors for AD, genetic risk factor such as possession of e4 allele of apolipoprotein E (ApoE4) is considered as a crucial risk factor. Moreover, dietary fat composition has also been concerned as an important factor for AD since cholesterol and blood-brain barrier functions are linked with AD. The primary genetic risk factor is ApoE e4 allele that encodes one of several proteins responsible for cholesterol transport and it is considered as foremost cholesterol transport proteins in the brain. For the progression of AD high level of serum/plasma cholesterol has been recommended as a causative factor. But this statement is debatable meanwhile brain cholesterol levels of AD patients are highly variable and cholesterol levels in serum/plasma and brain of AD patients do not consider cholesterol as a risk factor in AD. Indeed, APOE e4 is neither essential nor enough for the development of AD, it only serves as a synergistic and increases the risk of AD. Another prominent feature of AD is region-specific declines in brain glucose metabolism. The brain cells are totally different from other cells of the body, the brain cells cannot competently metabolize fats, therefore completely depends on glucose as an energy substrate. Consequently, inhibition of glucose metabolism can have intense effects on the brain functions. As a result hypo-metabolism observed in AD has just attained considerable attention as a probable target for interference in the disease progression. One propitious way is to maintain the regular glucose supply to the brain with ketone bodies from ketogenic diet represents a potent therapeutic for AD. Therefore the objective of this study was to analyze the relationship of the high dietary fat composition to the risk of developing AD by considering the impact of ApoE genotype.