Some cultures have
demonized alcohol while others have welcomed it. Modern research has confirmed
that over indulgence in alcohol is bad for you but also shown that moderate
drinking increases health and life expectancy. Most of the beneficial effects
appear related to the heart and circulation – but not all. Recently, positive
effects of alcohol have been shown for both Alzheimer’s disease and diabetes –
but these are less clear cut.
As is widely known, Alzheimer’s
disease has become a major problem in advanced societies, as life expectancy
has increased. At present, there is no cure for Alzheimer’s, although some
treatments can slow down its progress. Neural degeneration in Alzheimer’s
disease has been linked to the accumulation of the beta-amyloid protein
in brain cells. beta-Amyloid is derived from the larger APP protein
found in nerve cell membranes and clumps together forming plaques (see Fig. 1).
However, the most dangerous form of beta-amyloid may be smaller aggregates that block nerve
signaling rather than the larger clumps.
Figure 1 Conversion of APP to amyloid beta.
APP (amyloid precursor
protein) is located in the cell membrane. When APP is cut up it releases
amyloid beta (purple segment) as one of the fragments. This aggregates in
stages, eventually forming plaques. But the intermediate oligomers are probably
the most dangerous.
Alzheimer’s patients have
been exhaustively surveyed over the last couple of decades in the hope of
revealing environmental factors that may affect the disease. The earliest surveys
linking Alzheimer’s and alcohol were rather confusing. While occasional studies
suggested drinking alcohol increased the risk of Alzheimer’s, considerably more
surveys found drinking led to a decreased risk, and yet others found no
significant effect.
This confusion is not
really surprising – we already know that excessive drinking generally harms
your health whereas moderate drinking is good for you. Not surprisingly,
further analysis argues that excessive drinking makes Alzheimer’s worse but
that moderate drinking mitigates the effects of Alzheimer’s.
But there are yet more
complications. It is well known that men and women respond differently to
alcohol in some respects. A long term Norwegian study has been tracking around
40,000 participants since the 1980s. They found that moderate alcohol intake
has a positive effect on both Alzheimer’s and diabetes but that the protective
effect of alcohol was a lot more pronounced for men than women. The reason is
unknown. This finding is curious, since generally women are more sensitive to
the effects of alcohol.
As if this complication
was not enough, genetic factors are also involved. The most important concerns
apolipoprotein E. This protein helps control levels of fats and cholesterol in
the blood. It also affects removal of b-amyloid from the brain. There are three genetic
variants of apolipoprotein E (apoE). The one to avoid is apoE4, which predisposes
its carriers for Alzheimer’s. This has an allele frequency of 14% in the
population. It turns out that alcohol does not help those people who have apoE4
– indeed, if anything, alcohol has a negative effect.
Apparently, then, before
deciding how much to drink, you need not only to know whether you are male or
female but which apolipoprotein E genes you carry!
Getting back to the
positive alcohol effect - how does it work? Work from the last couple of years
shows that the smaller aggregates of b-amyloid can insert into the cell membrane where it
forms channels. These interfere with nerve cell signaling by letting calcium
ions (Ca2+) across the membrane. Alcohol opposes aggregation of beta-amyloid,
which decreases the number of channels damaging nerve cell action (see Fig 2).
APP (amyloid precursor
protein) is located in the cell membrane. When APP is cut up it releases
beta-amyloid (purple segment) as one of the fragments.
This aggregates in stages,
eventually forming plaques. But the intermediate oligomers are probably the
most dangerous.
