Scientists have discovered that Alzheimer's disease affects the brain in two distinct stages.

The most common form of dementia, Alzheimer's disease, involves a gradual decline of brain cells. This neurodegenerative disorder, first described in 1907 by German psychiatrist Alois Alzheimer, leads to impairments in memory, intellect, and emotional regulation. The condition is most frequently diagnosed in patients over the age of 65; however, significant brain damage occurs long before symptoms present themselves.

Previously, it was believed that the disease progresses in several stages characterized by cell death, inflammation, and the accumulation of proteins in the form of plaques. However, recent research published in the journal Nature Neuroscience has revealed that this disease alters the brain in two distinct phases. This discovery greatly enhances our understanding of the cellular processes observed as the neurodegenerative disease progresses.

Utilizing advanced genetic analysis techniques, researchers examined samples from over 3.4 million cell nuclei extracted from the middle temporal gyrus—a brain region involved in language processing and semantic memory—of 84 donors with Alzheimer's at various stages. The average age of the patients (33 men and 51 women) was 88 years, and the tissue samples were obtained post-mortem.

Rather than comparing with data from healthy individuals, the scientists arranged the donors along a pseudo-progression scale of the disease based on quantitative neuropathology and developed a multimodal map of brain cells. This map illustrates the cellular and genetic chronology of changes throughout the disease.

Thus, the team identified two distinct stages in the progression of the illness. The first phase is characterized by a slow accumulation of pathology and damage to specific types of cells, including inhibitory neurons. These changes disrupt neural circuits.

The second phase is marked by an exponential increase in pathological changes, including the loss of excitatory neurons and other subtypes of inhibitory neurons. At this stage, more extensive destruction occurs, accompanied by memory impairment and other symptoms.

The creation of a multimodal map of brain cells in Alzheimer's disease provides a better understanding of which cell populations and processes are involved in the development of the illness at different stages. This finding will also facilitate the development of new diagnostic methods and targeted therapies for this neurodegenerative disease, potentially capable of slowing or preventing brain damage.