Research Suggests Alzheimer’s Disease Causes Loss of Synaptic Function Rather Than Loss of Synapses

Research Suggests Alzheimer’s Disease Causes Loss of Synaptic Function Rather Than Loss of Synapses

Alzheimer’s disease has long been associated with the progressive loss of neurons and synapses; however, new research is challenging this view. A new study suggests that instead of loss of neurons and synapses, the disease causes loss of synaptic function.

The evidence comes from a joint study by researchers in Canada and France. The study was conducted on 171 patients with and without Alzheimer’s disease, at various stages of cognitive impairment.

Synaptic loss, plaques and neurofibrillary tangles are all associated with Alzheimer’s disease. The researchers investigated these hallmarks of Alzheimer’s disease by looking at synaptic markers in neocortical Brodmann area 9 (BA9), and evaluated the levels of vesicular glutamate transporters (VGLUT1&2), post-synaptic density protein of 95 kD (PSD95), glutamate uptake site (EAAT2), vesicular GABA/glycine transporter (VIAAT), synaptophysin, somatostatin (som) and choline acetyl transferase (ChAT).

The loss of neurons and synapses should result in decreases in these synaptic markers, yet the researchers found that was not entirely the case. Dementia caused by Alzheimer’s disease was only accompanied by a minor decline in neuronal and synaptic markers.

VGLUT1, PSD95, VIAAT, som, ChAT and synaptophysin expression levels decreased significantly as dementia progressed, although levels of VGLUT2 and EAAT2 were unaffected by dementia.

The decrease in synaptophysin was lowest (12%) and som was highest (42%), while the decrease in VGLUT1 was most strongly associated with dementia. However, using principal component analysis, the researchers were unable to differentiate the clinical dementia rating scale (CDR) groups from each other.

“Much to our surprise, in studying the fate of eight neuronal and synaptic markers in our subjects’ prefrontal cortices, we only observed very minor neuronal and synaptic losses,” said Dr. El Mestikaw from Canada’s Douglas Mental Health University Institute, who participated in the study.

The study suggests that the loss of synaptic markers is only weakly related to dementia caused by Alzheimer’s disease, and that it is a relatively late event in the progression of the disease. The loss of synaptic markers in BA9 was not linked to the loss of cognitive function.

Currently, therapeutic intervention in patients with Alzheimer’s disease has been focused on slowing down the rate of synaptic destruction; however, the new research suggests treatments for Alzheimer’s disease need to be rethought.

Dr. El Mestikawy said, “Based on our study, we are going to have to change our therapeutic approach.”

The study – Moderate Decline in Select Synaptic Markers in the Prefrontal Cortex (BA9) of Patients with Alzheimer’s Disease at Various Cognitive Stages – was recently published in Nature Scientific Reports.

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