Brain Inflammation May Occur 20 Years Prior to Alzheimer's Symptoms

Approximately twenty years before the first symptoms of Alzheimer’s disease appear, the brain may already be showing markers of inflammation in the form of higher levels of astrocytes, according to a new study at Karolinska Institutet in Sweden.

Astrocytes are specialized glial (support) cells involved in nervous system repair.

Alzheimer’s disease is characterized by the atrophy of brain neurons, especially those involved in memory. Exactly what causes the cells to die is still unclear, but many years before the first symptoms manifest, many pathological changes occur, such as the formation of amyloid plaques, the accumulation of tau proteins, and inflammatory changes that eventually degrade the points of contact between neurons.

However, exactly when these changes take place along this chain of events remains a mystery.

For the study, the researchers recruited family members of people with known Alzheimer’s mutations and therefore run a much higher risk of developing the disease. This allowed the researchers to watch for and examine any changes taking place during the very early stages. They also recruited patients with non-inherited, ‘sporadic’ Alzheimer’s disease as a comparison group.

All participants in the study underwent memory tests and scans using PET (positron emission tomography). PET allows radioactive tracer molecules to be introduced into the brain via injection into the blood.

Participants who carried the known mutations were found to have amyloid plaque and inflammatory changes almost twenty years before the estimated onset of memory problems. The number of astrocytes reached a peak when the amyloid plaque started to accumulate in the brain.

Furthermore, neuronal function, as measured by glucose metabolism, began to decline roughly seven years before the expected disease symptoms.

Participants from families with Alzheimer’s who did not carry any mutation showed no abnormal changes in their brain.

“Inflammatory changes in the form of higher levels of brain astrocytes are thought to be a very early indicator of disease onset,” explains principal investigator Professor Agneta Nordberg at the Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research at Karolinska Institutet.

“Astrocyte activation peaks roughly twenty years before the expected symptoms and then goes into decline, in contrast to the accumulation of amyloid plaques, which increases constantly over time until clinical symptoms show. The accumulation of amyloid plaque and the increase in number of astrocytes therefore display opposing patterns along the timeline.”

The findings reveal that the pathological processes that ultimately lead to Alzheimer’s disease begin many years before any outer symptoms occur, and that very early treatment is a possibilty. The researchers indicate that astrocytes may be a potential target for new drugs.

The research is published in the journal Brain.

Source: Karolinska Institutet