Does Alcohol Protect Against Alzheimer’s Disease?
By Kenneth Anderson, MA
Is Moderate Drinking Protective Against Alzheimer’s Disease?
Brain Changes with Alzheimer’s Disease
Amyloid Beta Plaques
We have known for more than a century that the brains of people with Alzheimer’s disease are filled with amyloid beta plaques and neurofibrillary tangles. Moreover, the brains of people with Alzheimer’s disease are severely atrophied due to the death of brain cells. Most researchers believe that the brain atrophy and death of brain cells found in Alzheimer’s disease is due to the effects of amyloid beta plaques and neurofibrillary tangles, although many details about this process remain unclear. It is also unclear whether amyloid beta plaques and neurofibrillary tangles contribute equally to the death of brain cells or if one of these is the primary cause.
Amyloid beta plaques result from the breakdown of amyloid precursor protein. Amyloid precursor protein exists in the form of little rods which pierce the cell membrane of neurons in the brain. Amyloid precursor protein is involved in the growth and repair of neurons and in the transport of chemicals inside the neuron, and hence, is essential for the proper functioning of neurons. The problem comes when old amyloid precursor protein needs to be broken down and recycled back into the cell. There are two pathways by which amyloid precursor protein can be broken down: one pathway is harmless, but the other is not.
In the first pathway, the enzymes alpha-secretase and gamma-secretase cut amyloid precursor protein into three pieces; all three pieces are easily broken down into smaller molecules which are recycled by the cell. In the second pathway, the enzymes beta-secretase and gamma-secretase cut amyloid precursor protein into three pieces; however, one of these three pieces is amyloid beta, which is sticky and likes to form clumps. Amyloid beta is a protein fragment which can consist of anywhere from 36 to 43 amino acids; however, the vast majority of amyloid beta is either 40 amino acids long or 42 amino acids long. The former is known as amyloid beta 40 and the latter is known as amyloid beta 42. Amyloid beta 40 is the more abundant of the two, but amyloid beta 42 is the more problematic. This is because amyloid beta 42 is the stickiest and has the greatest tendency to form clumps, which can grow into plaques.
Amyloid beta plaques are formed outside the neuron; they can disrupt neural signaling at the synapse and interfere with normal neuron functioning, leading to neuron death. Many researchers believe that amyloid beta plaques are also involved in the formation of neurofibrillary tangles.
Neurofibrillary Tangles
Unlike amyloid beta plaques, neurofibrillary tangles are formed inside the neuron. Neurofibrillary tangles result from the destruction of the neuron’s microtubules.
A microtubule consists of several long strands of protein tied together into a tube-shaped bundle by a protein molecule. An axon contains many microtubules which run from the cell body to the tip of the axon. Dendrites also contain microtubules, as does the cell body. Microtubules give the neuron its shape, and they are essential for the transport of molecules throughout the neuron. In the axon, the molecule which ties the protein strands together is known as Tau. When a phosphoryl group (i.e., a group consisting of one phosphorus atom and three oxygen atoms) attaches to a Tau molecule, this process is known as phosphorylation. Phosphorylation is a part of the normal functioning of Tau. However, when too many phosphoryl groups attach to the Tau molecule and when they attach in the wrong places, this is known as hyperphosphorylation. Hyperphosphorylation causes Tau to detach from the microtubules and form clumps; these clumps of Tau are known as neurofibrillary tangles. Hyperphosphorylated Tau is known as p-Tau. When p-Tau detaches from microtubules, these microtubules fall apart, and transport of chemicals in the neuron is disrupted, leading to neuron death.
Tests for Risk of Alzheimer’s Disease
Amyloid beta plaques and neurofibrillary tangles begin forming in the brain a decade or so before any of the signs or symptoms of Alzheimer’s disease appear. Today, we have several techniques for determining the presence of amyloid beta plaques and neurofibrillary tangles in the brain, enabling us to tell if someone is at risk of developing Alzheimer’s disease long before any of the signs or symptoms of Alzheimer’s disease appear.
Amyloid beta plaques and neurofibrillary tangles can both be detected by PET scans. Analysis of cerebrospinal fluid and blood plasma can also inform us of the existence of amyloid beta plaques and neurofibrillary tangles long before any signs or symptoms of Alzheimer’s disease appear.
One common test to detect the presence of amyloid beta plaques is to measure the ratio of amyloid beta 42 divided by amyloid beta 40 (Aβ42/40) in either cerebrospinal fluid or blood plasma. If amyloid beta 42 is forming clumps in the brain, very little of it escapes into the cerebrospinal fluid or blood plasma. Hence, a low value for the ratio of amyloid beta 42 divided by amyloid beta 40 (Aβ42/40) is indicative of amyloid beta plaques in the brain and means that the person is likely to develop or already has Alzheimer’s disease. If one is testing cerebrospinal fluid, it is also possible to test for the concentration of amyloid beta 42 instead of testing for the ratio of amyloid beta 42 divided by amyloid beta 40 (Aβ42/40). If one is testing blood plasma, however, only the ratio test is valid.
Other tests to tell if someone is at risk of Alzheimer’s disease involve testing the cerebrospinal fluid for the Tau proteins, which, as we saw above, bind the microtubules together. There are two tests which can be performed with Tau proteins in cerebrospinal fluid. One test involves measuring the amount of hyperphosphorylated Tau (p-Tau) present in the cerebrospinal fluid and dividing this by the amount of amyloid beta 42, giving us the ratio p-Tau/Aβ42. If this ratio is high, it means that many Tau proteins have broken free from microtubules, and the risk of forming neurofibrillary tangles is high. This test uses hyperphosphorylated Tau (p-Tau) which has a phosphoryl group attached at the 181st amino acid of the Tau molecule; it is sometimes referred to as the p-Tau181/Aβ42 test.
The other test which uses Tau proteins in cerebrospinal fluid to measure the risk of developing Alzheimer’s disease is the total Tau (t-Tau) ratio test; this test measures the ratio of all Tau molecules in the cerebrospinal fluid, both phosphorylated and nonphosphorylated, divided by Aβ42. This is known as the t-Tau/Aβ42 ratio. If this ratio is high, it means that many Tau proteins have broken free from microtubules, and the risk of forming neurofibrillary tangles is high.
The blood plasma Aβ42/40 is generally used as a screening test since it is the least invasive. If the blood plasma test is positive, the three cerebrospinal fluid tests are given to confirm the risk of developing Alzheimer’s disease. These tests are more invasive than the blood plasma test since they require a lumbar puncture. If these three tests are positive, a PET scan may be used to further confirm the risk of Alzheimer’s disease.
Does Alcohol Protect Against Alzheimer’s Disease?
It is generally agreed that heavy drinking increases the risk of and the progression of various types of dementia. It is, however, controversial as to whether or not heavy drinking increases the risk of Alzheimer’s disease. A 2024 review by Zahr found that alcohol use disorder increased the risk for dementia, but not necessarily Alzheimer’s disease. A 2023 review by Chandrashekar et al. found that heavy drinking aggravated Alzheimer’s disease, whereas light drinking tended to be protective against Alzheimer’s disease. Moreover, there is no consensus as to whether light to moderate drinking increases the risk of developing Alzheimer’s disease, decreases the risk, or has no effect at all.
Drouka et al. (2025) conducted a study of 195 subjects without dementia to see whether moderate drinking had an effect on risk for dementia. The average age of the subjects was 65. The 195 subjects were divided into three groups: there were 117 total abstainers, 27 occasional drinkers, and 51 light to moderate drinkers.
Occasional drinkers were defined as subjects who drank two standard drinks or less per week. Light to moderate drinkers were defined as subjects who drank more than two standard drinks per week. Heavy drinkers had been screened out before the study started. Heavy drinkers were defined as men who drank 1.7 or more standard drinks per day, or women who drank 1.1 or more standard drinks per day. A standard drink was defined as 14 grams of pure ethanol, the same as the US standard drink.
Subjects were given three cerebrospinal fluid tests for risk of Alzheimer’s disease: the amyloid beta 42 (Aβ42) concentration test, the total Tau ratio test (t-Tau/Aβ42), and the hyperphosphorylated Tau (p-Tau) ratio test (p-Tau/Aβ42).
The investigators found that amyloid beta 42 (Aβ42) concentration of light to moderate drinkers was significantly lower than that of abstainers, suggesting that light to moderate drinkers had a significantly greater risk of Alzheimer’s disease than abstainers. There were no significant differences between occasional drinkers and abstainers for this test.
There were no significant differences between the three groups for the total Tau ratio test (t-Tau/Aβ42).
There was no significant difference between light to moderate drinkers and abstainers for the hyperphosphorylated Tau ratio test (p-Tau/Aβ42). There was also no significant difference between occasional drinkers and abstainers for the hyperphosphorylated Tau ratio test (p-Tau/Aβ42) for unadjusted data; however, if the data were adjusted for age, sex and education, the p-Tau/Aβ42 ratio for occasional drinkers was significantly greater than the ratio for abstainers, suggesting that occasional drinkers had a significantly greater risk of Alzheimer’s Disease than abstainers.
The investigators also looked at the effect of the Mediterranean Alcohol-Drinking Pattern on risk of Alzheimer’s Disease. The Mediterranean Alcohol-Drinking Pattern involves moderate consumption of red wine with meals, and a high adherence to the Mediterranean Alcohol-Drinking Pattern has been shown to reduce mortality compared to abstinence or low adherence. However, the current study found that high adherence to the Mediterranean Alcohol-Drinking Pattern increased the risk of Alzheimer’s disease, based on the results of all three tests, the amyloid beta 42 (Aβ42) concentration test, the total Tau ratio test (t-Tau/Aβ42), and the hyperphosphorylated Tau ratio test (p-Tau/Aβ42).
Interestingly, a 2024 meta-analysis by Zarezadeh et al. found that the relationship between alcohol consumption and cognitive dysfunction and dementia was a J-shaped curve, with moderate drinkers showing the least cognitive dysfunction and dementia. This study, however, was not specific to Alzheimer’s disease.
A 2019 review by Anstey et al. found that light to moderate drinking was protective against all-cause dementia, Alzheimer’s Disease, and vascular dementia. A 2023 cohort study by Jeon et al. found similar results; this study used an insurance database of 3,933,382 South Koreans.
In summary, studies of the effect of moderate drinking and even heavy drinking on Alzheimer’s Disease are contradictory. It remains unclear whether alcohol might be protective against Alzheimer’s disease or a risk factor for Alzheimer’s Disease. So, does alcohol protect against Alzheimer’s Disease? The answer? Maybe.
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