2023-05-24 00:12:33
“Alzheimer’s Disease” 6000-person sample study: Is your dementia predestined? Rare reelin gene mutation once once more provides clues to protective mechanism (must read)
Like a detective story,When scientists are “hunting” for the “murderer” of Alzheimer’s disease, they always miss any clues.And these details, sometimes may be the key.In the large study of the Columbia-Boston Biomarker Study (COLBOS) at Massachusetts General Hospital, a man from Columbia who becameMedical Mystery!
In a large Colombian family of more than 6,000 living members, more than 1,200 of them live in Carrying the rare mutation E280A in the Presenilin 1 (PSEN1) genethe abruptlead to suffering from99.9% risk of early-onset Alzheimer’s，Mild cognitive impairment usually occurs around age 44, dementia develops at age 49, and more dies in their 60s. However,The man did not develop mild dementia until he was 72 years old and died of pneumonia two years later.
When scientists examined his brain, it was found that the manAmyloids and tangles of tau are scattered throughout the brain, yet the entorhinal cortex, a region critical to memory and navigation, is relatively unaffected by toxic tau tangles!
The study further found that,The man had a “rare mutation in the reelin protein”，May protect him from Alzheimer’s (reelin is important for the development of brain cells). After scrambling, it was discovered that the mutation, called “RELN-COLBOS,” helps reelin to hold its receptors tighter in the brain. This discovery intrigued researchers because mutations* in APO3 Christchurch (APOE3ch), which reduce the binding of apolipoprotein E (Apo E) to this receptor, also appear to protect the brain and delay the development of APO. occurrence of Alzheimer’s disease.
Scientists still don’t know the details of how the “RELN-COLBOS” mutation delays Alzheimer’s disease, but preliminary studies point to one of the causes of the disease-phosphorylated tau protein.currently known reelin reduces tau phosphorylation by activating Dab1 proteinand the study confirmed that the protective “RELN-COLBOS” mutation increased the amount of Dab1 in the mouse model, and wouldSignificantly reduced tau deposition in areas of the brain critical to memory.
Negative is positive?
Carrying mutations in the PSEN1 gene predisposes to Alzheimer’s disease，Carrying additional “RELN-COLBOS” or APOE3ch mutations, but reversed the situation ─ Although the brain will still be full of amyloid and tau protein deposits. The researchers said that the protection of only a small area of the brain is enough to maintain cognitive ability for 20 or 30 years. This will be a major discovery and surprise! In addition, the Colombian man’s younger sister also carries the “RELN-COLBOS” mutation, and her development of dementia was also delayed, which further highlights the importance of this mutation; in the future, scientists will continue to analyze other “RELN-COLBOS” mutations There are not many cases to get more clues and evidence.
* illustrate:
In 2019, a woman in the family was found in the large study “COLBOS” to carry two copies of the APOE3 gene variant (i.e. the APOE3ch variant) with many deposits of amyloid-like proteins in her brain but no tau protein tangles ; which delayed her Alzheimer’s disease by decades and allowed her to live into her 70s. The discovery prompted scientists to wonder whether genetic therapy might mimic this protection, or whether there were other unknown mutations that were also protective; hence, the above findings.
Further reading:“Alzheimer’s disease” FDA accelerated approval application rejected!! FDA Complete Response Letter (CRL) requested Lilly donanemab 12-month effectiveness and safety tracking data (must read)
Further reading:“Alzheimer’s disease” may reduce drug costs!! Lilly candidate rookie remternetug can remove amyloid plaques in the brain, but suspected side effects of brain edema?? (Read)
Source: Endpoints News, The Washington Post
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