Prof. Dr. Roland Brandt, Head of the Department of Neurobiology at Osnabrück University and Chairman of the Scientific Advisory Board of the Alzheimer Research Initiative: Alzheimer’s Dementia is the most common form of cognitive impairment and affects 60 to 70 percent of all dementia patients. The risk of developing Alzheimer’s increases sharply with advancing age. When looking closely at the brains of Alzheimer’s patients, changes can be observed inside and outside the cells.

First, in Alzheimer’s, the synapses as connection points between nerve cells change and might even be completely lost; communication between the nerve cells is thereby impaired. The cause is senile plaques, microscopically small deposits between the cells that consist mainly of clumped Beta-amyloid peptides, a cleavage product of a longer precursor protein. Alzheimer’s also occurs more frequently with increasing age because the production of intact proteins in the brain functions less well as age increases, and misfolded molecules can then stick together to form Plaques. In the early stages of Alzheimer’s, the impaired communication between nerve cells manifests itself in reduced Memory performance. This early impairment can be improved through training, and this is also where the new antibody therapies come into play, such as the first antibody drug approved throughout the EU, Leqembi (lecanemab), which aims to reduce the amount of senile plaques in order to slow the progression of the disease.

In the more advanced stage of Alzheimer’s disease, additional changes inside the nerve cells apply. Alzheimer’s fibrils, thread-like protein deposits, form inside the cells from aggregated tau proteins. These fibrils – or their precursors - cause the nerve cells to die. The Hippocampus and the entorhinal cortex, brain regions that play a key role in memory, are affected early on. Damage caused by the death of nerve cells generally cannot be reversed, as the regenerative capacity of nerve cells is very limited. As the damage increases, there is then a progressive impairment of cognitive performance, ultimately leading to complete disorientation. 

The comprehension of the Tau protein playing a key role in the death of nerve cells has developed in recent years. Previously, it was believed that senile plaques were primarily responsible for the disease. However, changes in the tau protein correlate much more strongly with the death of nerve cells than the plaques and are also measured in newly developed blood tests. Pathological changes in the tau protein also occur in diseases other than Alzheimer’s in which nerve cells die. This includes, for example, boxer’s encephalopathy, now usually referred to as chronic traumatic encephalopathy (CTE), which is caused by frequent head injuries. This ist also seen in professional American football players developing dementia at a very early age, as has been observed in the USA. Frequent heading in soccer could also pose a corresponding risk. Preventing the formation of tau aggregates is therefore also an important goal for new treatment options, and my team is also working on corresponding inhibitors that prevent the aggregation of tau and restore its normal function.

The death of nerve cells is also so dramatic because it causes further changes in the brain: Dying nerve cells reduce the production of acetylcholine, an important Neurotransmitter for mental performance. This in turn impairs communication between the nerve cells. This is where symptomatic treatments for Alzheimer’s disease come into play, such as acetylcholinesterase inhibitors like donepezil or galantamine. When nerve cells die, harmful substances are also released into the brain that can weaken it and cause inflammation. Glial cells such as astrocytes and Microglia play a role in this; these cells are found alongside nerve cells in the brain and have important supportive functions. However, glial cells can be a double-edged sword: On the one hand, they fight pathogens, while on the other hand, they can also cause damage to nerve cells, which then leads to further impairments. But it is not only inflammatory processes in the brain itself that play a role, the whole body is relevant: Inflammation in the peripheral system, for example caused by viral infections or surgical procedures, or, according to more recent studies, also by intestinal inflammation and even the oral microbiome, can contribute to the development of Alzheimer’s.

In recent years, awareness has also increased that Alzheimer’s is a disease in which lifestyle plays an important role. The risk of developing Alzheimer’s can be reduced through a healthy diet, avoiding excess weight, physical activity and mental stimulation. In this way, everyone can help to reduce their own risk of this terrible disease at least somewhat.

Recorded by Natalie Steinmann

Question first published on January 18, 2013

Question reanswered on August 23, 2026