Scientists have linked a rare gene mutation with protecting a woman from developing symptoms associated with Alzheimer’s disease.
Researchers say it could be the first known candidate for a gene that has the potential to be used in the development of interventions to halt the progression of the disease.
Some people who carry mutations in genes known to cause early onset Alzheimer’s disease do not show signs of the condition until a very old age.
Researchers found one such person in a study of 1200 individuals in Colombia for whom Alzheimer’s disease is extremely likely to develop owing to genetic predisposition.
The woman, from a large extended family with more than 6000 living members, did not develop mild cognitive impairment until her seventies – nearly three decades after the typical age of onset for those in her family.
Like her relatives, thousands of whom have showed signs of dementia in their forties, the patient carried the E280A mutation in a gene called Presenilin 1 (PSEN1).
This gene has been shown to cause early onset Alzheimer’s disease, according to the research published in the Nature Medicine journal.
Analysis showed the woman had a high degree of brain amyloid pathology, a hallmark of the disease, but did not present with symptoms associated with the disease.
Researchers found she has two copies of a variant of the APOE3 Christchurch (R136S) mutation.
They suggest this may have counteracted the detrimental effects of the PSEN1 mutation, and could have protected her against the disease.
In several experiments, they suggested mechanisms by which this mutation may exert its protective effects by impairing binding of APOE to certain sugars – called heparan sulphate proteoglycans (HSPG) – implicated in Alzheimer’s disease.
Co-author Dr Yakeel Quiroz, researcher at Massachusetts General Hospital, said: “This single case opens a new door for treatments of Alzheimer’s disease, based more on the resistance to Alzheimer’s pathology rather than on the cause of the disease.
“In other words, not necessarily focusing on reduction of pathology, as it has been done traditionally in the field, but instead promoting resistance even in the face of significant brain pathology.”
Co-lead author Dr Joseph Arboleda-Velasquez, of the Schepens Eye Research Institute of Massachusetts Eye and Ear, said: “This finding suggests that artificially modulating the binding of APOE to HSPG could have potential benefits for the treatment of Alzheimer’s disease, even in the context of high levels of amyloid pathology.”
Further research with larger samples is required to establish a definitive causal relationship between the mutation and protection from disease.Do you have an idea for a story?
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