Differences in the distribution of certain proteins and markers in the brain may explain why some people first experience vision changes instead of memory loss in Alzheimer's disease, finds a new study by UCL researchers.
Posterior cortical atrophy (PCA) is a rare form of Alzheimer's disease that, rather than causing problems with memory, leads to difficulties with reading, navigating, and recognizing objects. Studies suggest that one in 10 patients with Alzheimer's disease have a form which is visual, rather than memory led.
As well as presenting with unusual symptoms, individuals with PCA typically develop symptoms younger than most people with Alzheimer's disease, with onset usually in their 50s and 60s.
In a new study, published in Neuropathology and Applied Neurobiology and supported by Alzheimer's Society, researchers studied brain tissues from 26 people with PCA and 27 people with typical Alzheimer's disease who had donated their brains for research to the Queen Square Brain Bank at UCL.
The researchers looked at specific proteins and markers in different parts of the brain to see how they were affected.
They measured the amount and distribution of amyloid and tau (proteins related to Alzheimer's disease) and microglia (a key part of the brain's immune system involved in clearing damaged brain cells and proteins).
The study found that in people with PCA, the distribution of amyloid and tau was more widespread at the back of the brain (the parietal region), where visual information is processed and integrated.
They also found that microglial activity was elevated in PCA particularly in brain areas typically vulnerable to Alzheimer's disease, e.g. the sides of the brain (temporal region), the part of the brain characteristically vulnerable in typical memory-led Alzheimer's disease.
By contrast, the temporal region of patients with more typical memory-led Alzheimer's had the lowest amount of microglial activity and highest amount of tau compared to other brain regions.
This shows how the distribution of certain proteins and markers associated with Alzheimer's disease can lead to different symptoms.
Lead author, Dr Zeinab Abdi (UCL Queen Square Institute of Neurology) said: "These findings suggest that there is a link between the location of inflammation and accumulation of the proteins associated with Alzheimer's disease, which may explain why some people get memory symptoms while others have problems with vision."
The researchers hope that their findings will spur future research into the link between inflammation and accumulation of brain proteins in Alzheimer's disease and ultimately lead to targeted treatments and more tailored care for Alzheimer's patients.
By understanding the unique characteristics of rare, visual forms of Alzheimer's disease, we can move closer to developing targeted treatments that address the specific needs of each patient. This research highlights the importance of personalized approaches in tackling this complex disease."
Dr. Zeinab Abdi, Queen Square Institute of Neurology, University College London
Dr Richard Oakley, Alzheimer's Society Associate Director of Research and Innovation, said: "Dementia is the UK's biggest killer, with around one million people living with the condition. It's a highly complex illness and we desperately need to know more about what causes it, so we can beat it.
"There is much we don't yet understand about rarer and atypical forms of dementia. Without understanding the mechanisms that underlie these less common forms of Alzheimer's disease, we cannot develop accurate ways to diagnose or treat these diseases.
"That's why Alzheimer's Society is proudly funding studies like this one, which take a step forward in unpicking the complexity of a rare variant of Alzheimer's disease – revealing how protein accumulation and inflammation vary in brain regions compared to more typical forms of the disease.
"This type of work is critical to bringing us close to better diagnosis and new treatments so that no one is left behind, no matter what type of dementia they have.
"Research will beat dementia and that is why Alzheimer's Society is funding over £53 million in research, supporting over 400 researchers across the UK. Find out more at alzheimers.org.uk/research."
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