Heterogeneity in Alzheimer’s Disease Clinical Presentations

It is widely known that Alzheimer’s is a heterogeneous disease. Patients may present differently not only with varying ages of onset, but also with the type of clinical symptoms they may experience ranging from problems with memory or language, spatial difficulty, or problems with motor function. 

Renaud La Joie, PhD, Assistant Professor in Department of Neurology’s Memory and Aging Center at the University of California San Francisco recently presented at the University of Pennsylvania as part of the Institute on Aging’s Visiting Scholars Series to share how he and his team are working to better understand how these clinical symptoms relate to what is happening in the brains of Alzheimer’s disease patients using biomarkers and imaging. 

“What’s really unique about Alzheimer’s disease is that its characterized by the presence of two different types of abnormal proteins in the brain – amyloid plaques and tau pathology with many neurofibrillary tangles and other types of lesions,” said Dr. La Joie. “In our work, we are trying to bridge the heterogeneity we see in patients clinically to the proteins in the brain and what we [found] is, most of the variability across patients in terms of what type of symptoms they have and how old they are when they develop symptoms is related to the regional distribution and amount of tau pathology, not amyloid.”

Now, they are trying to understand when Alzheimer’s pathology happens, why some patients are more prone to getting pathology in certain brain areas versus the others. 

“It is going to take a lot of different multidisciplinary approaches to tackle this question, including genetics and basic science to understand different properties of different brain regions and why some regions are more vulnerable in some patients compared to others,” said Dr. La Joie. 

From the patient perspective, their hope is that this information will help the field better understand what kind of biomarkers can be informative at what disease stage. Right now, available biomarkers include imaging, measures from CSF, blood biomarkers, etc. but these measures are not all interchangeable and provide different types of information. 

“I think our research shows that tau PET, for example, can be very helpful to confirm the presence of Alzheimer’s pathology and also predict what may happen to the patient in the near future,” said Dr. La Joie. “The one thing that were really missing right now are biomarkers as a way of detecting other types of disease in the brain because we know that unfortunately, most patients with Alzheimer’s also have other types of pathologies in the brain and we think that all these pathologies together contribute to the clinical symptoms. So, right now we can only identify the presence of amyloid and tau, and everything else is kind of out of reach for us, but I’m really excited by some recent developments of biomarkers measuring other proteins like alpha synuclein and maybe in the future TDP-43.”


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