The most vulnerable brain cells with Alzheimer’s disease have been identified by scientists for the first time

Scientists have identified the most vulnerable brain cells for Alzheimer’s disease for the first time, in what has been dubbed the ‘holy grave’ of dementia studies.

The brain cells lie in an area called the entorhinal cortex, which controls memory, navigation and time comprehension, and are the first to be killed by the disease.

The researchers hope the findings could be used to develop a new and much more focused approach to developing therapies to slow or prevent the spread of Alzheimer’s disease.

The brain cells are particularly prone to toxic lumps, or ‘tangles’, of a protein called tau that destroys them from the inside.

Co-author Professor Martin Kampmann, of the Institute for Neurodegenerative Diseases, said targeting them could stop the disease in its pathways.

A study of brain tension found that the specific group of cells disappears very early – followed by a similar subset in the forward facial gyrus.

This is an area of ​​gray matter that relies on higher mental functions such as thinking, problem solving, planning and working memory – used in the performance of tasks.

The findings published in Nature Neuroscience are a ‘sacred tomb’ of dementia study.

Dr. explained. Kampmann: ‘We know which neurons die first in other neurodegenerative diseases such as Parkinson’s disease and motor neurone disease – but not Alzheimer’s.

‘If we understood why these neurons are so vulnerable, we might be able to identify interventions that could make them, and the brain as a whole, more resistant to the disease. . ‘

Alzheimer’s is caused by tau and amyloid – another inflammatory protein that builds up into pests, or lumps, outside brain cells.

Tau is said to be a ‘bullet’. The team at the University of California at San Francisco says some brain cells undergo years before symptoms develop – opening a ‘window of opportunity’.

Co-author, Professor Lea Grinberg, said: ‘The belief in the field has been that once these waste proteins exist, it is always a‘ game over ’for the cell.

‘But our laboratory has found out that’s not true.

‘High levels of tau go well in the progression of the disease in some cells, but for some reason they do not die.

‘It has become an important question for us to understand the specific factors that leave some vulnerable cells to Alzheimer’s pathology, while other cells appear to be able to resist for years, if not decades. ‘

The researchers examined print from two brain banks of dozens of people who had died at varying degrees of Alzheimer’s in the US and Brazil.

An invention allowed the single-nucleus RNA sequence to then establish groups based on gene activity patterns.

In both the entorhinal cortex and the anterior frontal gyrus, these vulnerable cells were identified by the expression of a protein called RORB.

Under a microscope, they confirmed that these neurons die early in the disease. They also collect tau tangles earlier than neighbors without RORB.

Co-author Kun Leng, a PhD student in Professor Kampmann’s laboratory, said: ‘These findings support the notion that erection is a vital driver of neurodegeneration.

‘But we also know from other data from the Grinberg laboratory that not all cells that build these collections are equally susceptible.’

He plans to continue looking at factors that underlie the selective vulnerability of RORB neurons using gene editing technology developed by the Kampmann laboratory.

It is unclear whether RORB itself causes selective cell vulnerability. But the protein provides a valuable new molecular ‘treatment’.

This will help you understand what makes these cells prone to Alzheimer’s – and how they may recur.

Co-author Kun Leng, of the University of California at San Francisco, said: ‘Our discovery of a molecular identifier for these vulnerable selective cells allows us to examine in detail why they are compliant. to pathology – and what could be done to make it more sustainable.

‘This would be a completely new and much more focused approach to developing therapies to prevent or prevent the spread of Alzheimer’s disease.’