Elevated tau protein levels impair memory function in AD only when amyloids also high

Large amounts of tau proteins in the brain affected memory function only when amyloid protein burden was also high in those with Alzheimer’s disease, data suggests in a study published in Brain.

“It has long been known that deposits of tau proteins in the so-called hippocampus and in neighboring brain areas impair memory,” Emrah Düzel, MD, director of the Institute of Cognitive Neurology and Dementia Research at Otto von Guericke University in Magdeburg, Germany, said in a release from the institute.

“In the case of amyloid, on the other hand, no clear relationship to memory performance has been found to date. For this reason, among others, it is debated whether it makes sense at all to target amyloid therapeutically. Our current results suggest that this could indeed be helpful for memory function in the early stages of the disease.”

Düzel and colleagues conducted a cross-sectional analysis of data from 235 participants in the DZNE-Longitudinal Cognitive Impairment and Dementia Study, aged 60 years and older, across 10 study sites in Germany. The group included cognitive-normal adults, as well as those with mild or moderate memory problems.

Researchers assessed participants’ cerebrospinal fluid for levels of amyloid and tau proteins and evaluated memory and brain activity with functional magnetic resonance imaging (fMRI), during which participants memorized photographic images while brain activity in the hippocampus was monitored.

Data analysis revealed that when amyloid protein levels were beyond the pathological threshold, higher levels of tau protein were observed in the CSF, which was linked with poorer memory performance and a reduction in hippocampal activity.

“In other words, high load by both proteins was the likely cause of memory impairment. This relationship has not been demonstrated in previous studies,” Düzel said in the release.

“This raises the possibility that in the predementia stage of Alzheimer’s disease, removing the negative impact of amyloid pathology could improve memory and hippocampal function even if the amount of tau-pathology in CSF is not changed, whereas reducing increased CSF tau-pathology in amyloid-negative individuals may not proportionally improve memory function,” Düzel and colleagues concluded.

References:

Duzel E, et al. Brain. 2022;doi:10.1093/brain/awab405.

Press Release.