An international team of researchers has shed new light on the neurodegenerative process in Alzheimer’s disease (AD), focusing on a unique group of neurons called the isodendritic core. In a recent publication in Alzheimer’s & Dementia, the team discusses evidence for a neuronal mechanism upstream of amyloid, which may be the primary driver of AD.
Isodendritic core neurons, which have a distinct origin from other brain neurons, have previously been identified as particularly susceptible to damage in AD. These neurons, located deep in the brain, are responsible for arousal and sleep-wake cycles and are not directly related to higher cognitive functions.
The authors note that while amyloid Alzheimer’s Disease plays a significant role in AD once it has progressed, it is not present in these neurons during the early stages. Instead, damage to these neurons triggers a retaliatory mechanism that, in adulthood, is detrimental rather than restorative.
The pivotal molecule responsible for this process is a bioactive 14-mer peptide, T14, which selectively activates a single target receptor. In the mature brain, T14 leads to neuronal death and initiates a detrimental snowball effect that worsens over time.
The researchers suggest that this mechanism may explain the long-term lag of 10 to 20 years between neuronal loss and the onset of cognitive impairment in AD. Furthermore, they propose that T14 could be used as a pre-symptomatic biomarker for AD, as it can be detected at an early stage of the disease.
In summary, this review offers a new perspective on the neurodegenerative process in Alzheimer’s disease, focusing on the role of isodendritic core neurons and the detrimental effects of the T14 peptide. This novel mechanism may provide valuable insights into the early stages of AD and potential new targets for therapeutic interventions.
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1. Source: Coherent Market Insights, Public sources, Desk research
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