Alzheimer’s disease (AD) is the most common form of dementia, showing an increasing rate of morbidity in the elderly population over the past few decades. AD pathology is characterized by the deposition of tau-tangles and accumulation of amyloid-β (Aβ), although it remains unclear whether these accumulations are a consequence or cause for AD.
In a report published in a journal of Neuropharmacology a team of researchers in China hypothesized that increased apoE in the brain may be an effective therapeutic strategy for AD. This so called apolipoprotein E (apoE) main function is as cholesterol carrier in the brain which is an essential component for axonal growth, synaptic formation and remodeling. The hypothesis is based on evidence that the excessive accumulation of Aβ in the brain is not due to aberrant Aβ production, but the result of poor Aβ removal from the brain combined with evidence suggesting that apoE enhances the break-down of this peptide.
In humans three major genetic forms of the protein apoE (E2, E3 and E4) have developed. In Alzheimer’s disease (AD) there is a particular strong association of apoE e4 form and disease prevalence. Interestingly, the apoE protein levels in cerebrospinal fluid and plasma tend to be lower in APOE e4 carriers and patients with AD. This suggests that lower levels of total apoE exhibited by the APOE e4 carriers may contribute to disease progression. Thus the researchers hypothesized that increasing apoE levels in all APOE genotypes may prevent or slow progression of AD through acceleration of Aβ removal.
They set out to identify novel compounds that can increase apoE levels and performed an in-vitro drug screen with immortalized astrocytes and primary astrocytes against a natural compound library. They found that quercetin can significantly increase apoE levels by inhibiting apoE degradation. Next they explored whether these effects can be also found in-vivo in an Alzheimer disease mouse model (5xFAD).
Male and female 5xFAD mice were orally fed on daily basis, for 10 days, with 500mg/kg/day quercetin. The researchers found that quercetin increases brain apoE levels and reduces Aβ levels in the cortex of the amyloid model mice.
It should be noted that observations in mouse models of AD might not necessarily extrapolate to humans. Nevertheless, these results suggest that lower levels of total apoE as seen by APOE e4 carriers may contribute to disease progression and that increases in all APOE level genotypes may prevent or slow progression of AD.
While not specifically mentioned in this publication a study into ApoE genotype and responsiveness to dietary factors noted that, based on a review of studies in humans, the beneficial effects of quercetin were observed in individuals carrying the e3 allele (but not in e4 carriers indicating apoE3 is a more flexible and responsive). A table of population distribution for genotypes and AD occurrence from wikipedia suggests that the e3 variant is the clear majority of the population.
Finally to gain perspective we calculate the Human Equivalent Dose (HED) for the quercetin diet given to the mice. The FDA has specified guidelines for this conversion to Human Equivalent Dose (HED). Using this guideline 500 mg/kg dosing in mice translates into a HED of approx. 40mg/kg. Or into 2.8gram daily quercetin dose for a person weighing 70kg. Typical supplements on the market have serving sizes of 500mg.