Lay summary by Hollie Wareing, reviewed by Dr Scott Allen and by a Dementia lay panel.
Background
Alzheimer’s is an incurable disease affecting millions worldwide, with the underlying cause remaining unidentified. The main symptoms of Alzheimer’s are memory and thinking ability loss, leading to a disruption of daily life. One crucial piece of this puzzle are proteins called Amyloid-β (Aβ) and Tau, which build up in the brains of people with Alzheimer’s. These proteins are used to diagnose and are monitored by fluid/brain biomarkers, which suggest that Aβ build-up happens before Tau, particularly in the earlier stages. However, not everyone with Aβ in the brain develops detectable early symptoms of the disease and these individuals are commonly referred to as cognitively unimpaired (CU). The authors believe that why some people with Aβ remain healthy while others develop Alzheimer’s are due to other processes which can cause damage to the brain.
Astrocytes act as the brain’s support team, protecting and helping nerve cells to function. However, in Alzheimer’s, astrocyte function can be disrupted and cause damage to surrounding nerve cells by becoming “reactive”. Previously studies show that reactive astrocytes are commonly found in CU individuals, with other studies showing that they are linked with the function of both Aβ and Tau.
Why is the study important?
In Alzheimer’s, treatments that slow down the disease work best when started early. Finding reactive astrocytes and Aβ in your brain could be an early sign that something’s not quite right. This is important for the development of new ways to predict who could get Alzheimer’s and give the possibility for future therapies.
What did the authors do and how did they do it?
The authors looked at data from 1,016 CU individuals, splitting them into two main groups; negative reactive astrocytes (Ast-) and positive reactive astrocytes (Ast+). The authors used markers to detect Aβ, Tau, and reactive astrocytes at the same time to understand the connection.
What are the results?
Overall, this study found an important link in Alzheimer’s: a connection between Aβ, reactive astrocytes and Tau levels, vital for the disease progression. Firstly, no difference in Aβ levels were found in either group. Secondly, those with both Aβ and reactive astrocytes had increase Tau levels than those with Aβ but not reactive astrocytes. Finally, this connection is stronger in men, though that doesn’t mean men are prone to Alzheimer’s; it suggests treatment responses may differ. The authors conclude that reactive astrocytes could be an early warning sign of Alzheimer’s in the brain for individuals who don’t develop initial symptoms until later stages. It reveals the connection between Aβ and tau proteins, guided by reactive astrocytes while highlighting gender differences.
What do the findings mean going forward for people with the disease?
The results suggest that abnormal astrocyte reactivity has the potential to be placed as an early upstream event in AD, and developed as an earlier biomarker to detect and understand AD progression further.
This study can be found at:
Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease | Nature Medicine
Paper Title:
Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease
Author List:
Bruna Bellaver and Tharick A. Pascoal