Neuroimaging can identify start and location of amyloid plaques in living brain.


Primary progressive aphasia (PPA) is a form of dementia characterized by degeneration of the language network.  In the early stages, PPA is associated with a left-lateralized pattern of cortical atrophy most commonly leading to frontotemporal degeneration, followed by Alzheimer’s disease.  PPA patients with Alzheimer’s disease generally show a different pattern of neurofibrillary tangles than beta-amyloid plaques, with varying distribution in the brain.
However, previous amyloid imaging has yielded conflicting conclusions concerning the position and start of the toxic build-up of amyloid protein in PPA.  Now, a study from researchers at Northwestern Medicine shows that the toxic build-up of amyloid protein is greater on the left side of the brain, the site of language processing, than on the right side in individuals living with PPA.  The team state that by understanding where these proteins accumulate first and over time, researchers can better understand the course of the disease and where to target treatment.  The study is published in the journal Annals of Neurology.

Previous studies show that amyloid accumulation in the brain could only be studied after an individual with Alzheimer’s disease had died. This snapshot in time was after the disease had run its full course, and amyloid had spread throughout the entire brain. The current study uses a new technology called Amyloid PET Imaging to study the build-up of the toxic amyloid during life in the brains of PPA patients.

The current study scanned 32 PPA patients, 19 of which had high amounts of amyloid and were likely to have the Alzheimer’s pathology. They were compared to 22 people who had Alzheimer’s memory-based dementia. Results show that those with the memory dementia had the same amount of amyloid on the left and right side of the brain.

Data findings using Amyloid PET Imaging show that the toxic amyloid protein was distributed differently in people that had the PPA language dementia versus the memory dementia in the early stages. Results show that there was more amyloid in the left hemisphere parietal region of individuals with PPA compared to those with Alzheimer’s memory dementia.

The lab state that, to their knowledge, this is the first study to examine and compare beta-amyloid buildup in the brain using the Amyvid amyloid PET imaging tracer between individuals with PPA and those with Alzheimer’s memory dementia. They go on to note that both types of dementia can be caused by an accumulation of beta-amyloid, an abnormal toxic protein in the brain.

The group explain that the recent ability to peer into the brain of living individuals with PPA, provides important new insights into the beginning stages of this disease, which results in language loss, when it is caused by a buildup of a toxic protein found in Alzheimer’s disease.  They go on to add that their research also offers additional insight into why PPA causes people to lose the ability to express themselves and understand language.

The team surmise that their new technology is very exciting for Alzheimer’s research, as not only can it tell if a person is likely or unlikely to have Alzheimer’s disease causing their PPA, it can also identify where it is in the brain. For the future, the researchers state that by understanding what the brain looks like in the beginning stages of Alzheimer’s, it is hoped this will enable the ability to diagnose people earlier and with better accuracy.

Source: Northwestern University

 

Negatively-stained TEM image of amyloid-like fibrils.

Negatively-stained TEM image of amyloid-like fibrils.

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