© Magnific
August 4, 2026
Dr. Andrea Gartenbach
he biological changes that can eventually lead to Alzheimer's often develop over decades. Dr. Andrea Gartenbach explains how sleep, metabolism, vascular health, and inflammation influence the risk of the disease.
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We talk about Alzheimer's mostly when people begin forgetting names, lose their sense of orientation, or when loved ones notice changes in their personality. From a medical perspective, however, the story begins much earlier. The biological changes that can eventually lead to Alzheimer's dementia often develop over many years — sometimes decades — before the first symptoms appear. The greatest misconception, then, may be confusing the disease with the moment of its diagnosis.
Alzheimer's doesn't appear suddenly. While life seems to proceed as normal, the brain's energy supply, protein processing, immune response, and vascular function change gradually. The brain can compensate for these burdens for a long time. Only when its reserves and repair mechanisms are no longer sufficient do disturbances in memory, orientation, or language become noticeable.
This is precisely where the opportunity for prevention lies: not waiting until cognitive abilities are lost, but understanding the processes that keep a brain resilient over decades.
Medicine has long explained Alzheimer's primarily through two proteins: beta-amyloid and tau. Beta-amyloid can accumulate outside nerve cells to form plaques; pathologically altered tau forms fibrous structures inside the cells.
Both are characteristic features of the disease and play an important role in its development. They alone, however, do not explain why one person develops the disease while another remains cognitively stable for a long time despite detectable deposits, or why known risk factors such as high blood pressure, diabetes, sleep disorders, or physical inactivity influence the course of the disease.
Dr. med. Andrea Gartenbach, specialist in Internal and Functional Medicine, expert in Longevity, and former competitive athlete
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Our current understanding is therefore broader. Alzheimer's is a disease of the brain whose development is shaped by many interconnected biological systems. Energy metabolism, vascular health, immune regulation, metabolism, sleep, genetic predisposition, and environmental factors are all intertwined.
This does not mean that amyloid and tau are unimportant. It means we must view them within a larger context. What determines health or disease is not a single cause, but the sum of burdens — and the brain's capacity to compensate for them.
Energy is a central factor. The brain accounts for only about two percent of our body weight, yet requires approximately one fifth of the energy the body consumes at rest. Billions of nerve cells communicate with one another every second. Remembering, planning, learning, and moving are all biologically intensive processes. Even small, long-lasting disruptions in energy supply can therefore undermine the stability of neural networks.
This is where the mitochondria come in. Often called the powerhouses of the cell, they produce ATP from nutrients — the energy carrier that cells need for almost all functions. But mitochondria do far more than that.
They influence calcium balance, the response to oxidative stress, inflammatory processes, and whether a damaged cell is repaired or broken down. In the brain, they are crucial in determining how resilient nerve cells remain and how well synapses — the contact points between nerve cells — function.
Energy metabolism can already change in the early stages of Alzheimer's disease. Certain brain regions metabolize glucose less efficiently before significant memory problems arise. This does not mean that Alzheimer's is simply an energy deficit. It does show, however, how closely the disease is linked to the metabolic health of the brain.
When mitochondria produce less energy while simultaneously generating more reactive oxygen species, cells come under stress more easily. Repair processes slow down, synapses lose stability, and nerve cells become more vulnerable to additional stressors.
The brain's immune system is closely linked to energy metabolism. Microglia play an important role here. They belong to the glial cells — a collective term for cells that nourish, protect, and support the function of nerve cells. Microglia are, in a sense, the immune and cleanup cells of the brain. They detect damaged cell components, remove waste products, and assist in repair processes.
Problems arise when microglia remain persistently activated. Chronic low-grade inflammation, metabolic disorders, vascular damage, or sustained oxidative stress can put them into a state of constant alert. They then release pro-inflammatory signaling molecules and can activate pathways such as the NLRP3 inflammasome.
This protein system is part of the innate immune defense and normally helps detect dangers quickly. But if it remains chronically active, the protective response itself can become a burden on nerve cells. This persistent inflammatory state in the brain is known as neuroinflammation.
This makes clear why Alzheimer's cannot be viewed in isolation from the rest of the body. Obesity, insulin resistance, diabetes, smoking, chronic stress, and physical inactivity increase inflammatory and metabolic burden through various pathways. They do not automatically cause Alzheimer's, but they can alter the biological environment in which the brain ages.
Vascular health is equally important. The brain is supplied by an extraordinarily dense network of tiny blood vessels, through which oxygen and nutrients reach the nerve cells. The inner lining of these vessels is called the endothelium.
A healthy endothelium ensures that blood vessels dilate as needed, blood flows unimpeded, and inflammatory and coagulation processes remain controlled. In endothelial dysfunction, this protective layer no longer functions optimally. The vessels respond less effectively, blood flow can be impaired, and inflammatory processes in the vessel wall increase.
This is particularly relevant for the brain. When microcirculation — the blood flow through the smallest vessels — diminishes over the years, sensitive brain regions receive less oxygen and energy. In addition, the blood-brain barrier, which shields the brain from harmful substances in the blood, can become more permeable. High blood pressure, diabetes, and lipid metabolism disorders all accelerate this process. Vascular medicine and neurology therefore cannot be meaningfully separated when it comes to Alzheimer's prevention.
Another key pillar is sleep. It is not a passive pause, but a phase of intensive biological activity. Memories are consolidated, neural networks are reorganized, hormones are regulated, and immune processes are coordinated. During sleep, the exchange of fluid in the brain also changes.
The glymphatic system plays a role here — a transport and cleansing system through which cerebrospinal fluid flows along blood vessels through the tissue, carrying away dissolved metabolic waste products.
Astrocytes are among the cells involved. These star-shaped glial cells supply nerve cells, regulate the chemical environment in the brain, and support fluid exchange. Experimental studies show that glymphatic flow and the removal of certain waste products are closely linked to sleep and neuronal activity.
Beta-amyloid and other proteins can also be transported away via these pathways. How strongly this mechanism operates in humans during individual sleep phases is still under investigation; the evidence is not consistent on all points. What is undisputed, however, is that chronically poor sleep is associated with a higher risk of cognitive decline and has an adverse effect on inflammatory, metabolic, and vascular processes.
This brings us full circle back to amyloid and tau. Beta-amyloid also forms in the healthy brain. It becomes problematic when production, processing, and removal are persistently out of balance. Amyloid can then accumulate between nerve cells and promote further changes.
Tau normally fulfills an important structural function within the nerve cell: it stabilizes the small transport rails along which nutrients and cell components are moved. When tau is pathologically altered, it detaches from these structures, clumps together, and disrupts transport within the cell. As the disease progresses, synapses and ultimately nerve cells are lost.
It would, however, be too simplistic to describe amyloid either as a meaningless byproduct or as the sole cause. More likely is a complex process in which amyloid, tau, inflammation, vascular changes, and disrupted energy metabolism mutually reinforce one another.
Which mechanism dominates first can vary from person to person. This is precisely why we need a medicine that not only names a diagnosis, but interprets each individual's risk profile.
An important part of this profile is genetics. The best-known genetic risk factor for the common, late-onset form of Alzheimer's is APOE. The gene contains the blueprint for apolipoprotein E, a protein that transports fats and cholesterol. In the brain, cholesterol is by no means merely a problematic substance. It is an essential component of cell membranes and synapses, and is needed for repair and communication between nerve cells.
There are three common variants of APOE: ε2, ε3, and ε4. APOE ε3 is the most common. APOE ε2 is associated on average with a lower Alzheimer's risk, and APOE ε4 with a higher one. One copy of ε4 increases the risk; two copies increase it further. Crucially, however, APOE ε4 is not a diagnosis.
Many carriers never develop the disease, and Alzheimer's can also occur without ε4. The gene describes a biological vulnerability, not a person's future.
This distinction is central. Genetic risks never manifest in a vacuum. Blood pressure, metabolism, exercise, sleep, smoking, hearing, education, social engagement, and other factors all influence how the brain ages. Some of these influences begin as early as childhood or middle age.
The current Lancet Commission concludes that nearly half of all dementia cases worldwide could theoretically be prevented or delayed if known modifiable risk factors were consistently addressed. This is not a promise that every dementia can be prevented. It is, however, a strong argument for thinking about prevention much earlier and more comprehensively.
This also calls for a close look at lipid metabolism. ApoB, apolipoprotein B, is found on all lipoprotein particles capable of depositing cholesterol into vessel walls. Such particles are referred to as atherogenic because they promote the development of atherosclerosis — that is, deposits and inflammation in the arteries.
LDL belongs to these particles, but other cholesterol-containing transport particles also carry ApoB. The ApoB value therefore approximates how many potentially vessel-damaging particles are circulating in the blood, and can reflect cardiovascular risk more precisely than cholesterol levels alone.
ApoB is not an independent diagnostic marker for Alzheimer's. However, a chronically unfavorable lipid metabolism can promote arteriosclerosis, small vascular damage, and reduced blood flow to the brain. In older people, Alzheimer's-typical changes and vascular damage frequently coexist.
Those who want to reduce their risk of dementia should therefore pay attention not only to memory, but equally to blood pressure, blood sugar, blood lipids, physical activity, and vascular health.
Diagnostic options are also evolving. Blood-based biomarkers can now provide indications of Alzheimer's-typical changes. Phosphorylated tau in particular — especially p-tau217 — is approaching the predictive power of established methods such as cerebrospinal fluid analyses or PET imaging in well-studied clinical settings.
Other markers provide complementary information: neurofilament light chain, or NfL for short, indicates nerve cell damage but is not specific to Alzheimer's. GFAP reflects astrocyte responses and can be elevated in various brain diseases.
These tests represent a major advance, but they require context. A single value cannot replace a thorough medical history, cognitive assessment, imaging, or specialist interpretation. In people without symptoms in particular, untargeted screening is not currently recommended as a general practice. An abnormal biomarker does not automatically mean that dementia will develop, and a normal value does not rule out all other causes of cognitive problems.
This is precisely where precision medicine begins. It does not mean collecting as much data as possible. It means gathering the right data at the right time and interpreting it in context. For one person, vascular risks may be the primary concern; for another, it may be sleep apnea, insulin resistance, chronic inflammation, hearing loss, or a genetic predisposition.
Often, several factors act simultaneously. A sound prevention strategy therefore does not rely on a universal protocol, but on medically informed prioritization.
This includes remarkably classic measures: consistently managing blood pressure, optimizing metabolism and lipids, regularly training endurance and strength, not smoking, diagnosing sleep disorders, addressing hearing loss, and avoiding social isolation.
Exercise works on multiple levels. It improves circulation and insulin sensitivity, stimulates the formation of new mitochondria, and promotes BDNF, a growth factor that supports the adaptability and connectivity of nerve cells. Muscle tissue, too, is far more than just an organ of movement. It improves glucose uptake, releases signaling molecules, and in doing so contributes to the metabolic and inflammatory regulation of the entire body.
Prevention does not thereby become spectacular or simple. It becomes more precise. It does not begin with a single supplement or a new test, but with the question of which biological systems in a given person are most in need of protection and which measures offer the greatest evidence-based benefit. Measurement alone is not medicine. What matters is the interpretation — and the action that follows from it.
Not every case of Alzheimer's disease can be prevented. Acknowledging this is part of responsible preventive medicine. But we can identify risks earlier today, treat many contributing factors in a targeted way, and potentially delay the onset of cognitive decline by years. Precisely because the disease begins long before the first symptoms appear, we cannot afford to wait until memory loss becomes visibly apparent.
Prevention does not only mean adding more years to life. It means protecting those years with clarity, independence, and mental presence. The next article turns its focus to women.
They are more frequently affected by Alzheimer's, yet for a long time research and prevention failed to examine them with sufficient nuance. The role played by estrogen, perimenopause, brain metabolism, and individual hormonal biology is therefore not a peripheral issue in women's health, but a central part of modern Alzheimer's prevention.
