For some time, scientists have believed that an abnormal, toxic molecule called amyloid-β is the key mediator of the pathology of Alzheimer’s disease. Although examinations of the brains of aged adults and those with the disease have shown that amyloid-β accumulates and forms clumps outside of cells, contributing to the formation of plaques, when it starts to build up has been unclear. Now, new research has found that it starts to accrue inside certain key populations of nerves in people as young as 20, which is significantly younger than scientists believed.

“Discovering that amyloid begins to accumulate so early in life is unprecedented,” lead researcher Changiz Geula said in a news release. “This is very significant. We know that amyloid, when present for long periods of time, is bad for you.”

Neurodegenerative diseases, such as Alzheimer’s or Parkinson’s, are characterized by a loss of neurons in certain brain regions, such as the basal forebrain. Cells in this area are known to be involved in memory and attention, both of which are affected in these disorders. Despite years of research, it is still unclear what precisely is causing these cells to die; however, several lines of evidence have indicated that a disruption to the balance of calcium within these cells could be playing a role.

But what is causing calcium levels to go awry? Given that the major risk factor for Alzheimer’s is age, potential mechanisms must be age-related, such as a gradual increase in something that prevents calcium from being able to get out of cells. Since studies have demonstrated a relationship between amyloid-β—which builds up outside cells in aged and Alzheimer’s brains—and calcium dysregulation, scientists wondered whether amyloid-β accumulates inside basal forebrain cells as we age, and also in those with Alzheimer’s.

To find out more, scientists from Northwestern University examined 50 brains from three groups of deceased individuals: cognitively normal individuals between the ages of 22 to 66; individuals without dementia between the ages of 70 to 99; and those with Alzheimer’s between the ages of 60 to 95.

As described in Brain, they found that amyloid-β does indeed begin to accumulate inside neurons of the basal forebrain during adulthood and continues to do so throughout our lives. Furthermore, the same buildup was not observed in other brain areas investigated. But what was perhaps most surprising was the observation that small, toxic clumps of this protein were present in very young adults in their 20s despite having normal cognitive function. These clumps were also found to increase in size as we age and in those with Alzheimer’s.

According to the researchers, these small clumps could be contributing to neuronal death in a number of ways. For example, studies of brain cells exposed to these clumps have shown that they cause excess amounts of calcium to begin to seep inside the cell, which can trigger cell death. Alternatively, the amyloid may get secreted out of the cell and encourage the formation of the characteristic plaques seen in the brains of those with Alzheimer’s. The researchers would therefore like to continue this work by investigating how internal amyloid could be contributing to neuronal damage.