Imaging is a Powerful Weapon in the War on Alzheimer's Disease

Tuesday, Dec. 03, 2019

Researchers and clinicians have worked for decades examining Alzheimer's Disease (AD), yet despite making significant progress in identifying factors that contribute to the development of AD, no one has successfully developed a disease-modifying medication.



New Horizons lecturer Andrew Saykin, PsyD, the Raymond C. Beeler Professor of Radiology and Imaging Services and professor of medical and molecular genetics at Indiana University (IU) School of Medicine, presented a look at AD research with a focus on prevalence, risk factors and biomarkers.

"Continued work in the field is evolving toward precision medicine for AD with the ultimate goal of prevention, therapeutic development and an understanding of the fundamental mechanisms needed to achieve this goal," Dr. Saykin said.

According to an annual report released by the Alzheimer's Association, AD is the sixth leading cause of death in the U.S. affecting nearly 6 million Americans and many more worldwide. "Annual costs are estimated to be nearly $300 billion and all of these figures will skyrocket given the aging population if we don't intervene," Dr. Saykin said.

After presenting a comprehensive list of known risk factors such as age, family history and genetics including the APOE gene, Dr. Saykin said the story of AD goes back 112 years to Alois Alzheimer who identified the mental deterioration of a woman in her 50s who had what became known as senile plaques in her brain.

Sharing imaging of amyloid beta plaques on molecular PET and tau PET, Dr. Saykin said, "On reflection of the incredible contribution of neuroimaging to this area, it's a transformative development to look at what was only visible before in brain tissue in vivo and potentially years before diagnosis."

Looking at the progress that has been made in the years since AD was first described, Dr. Saykin referred to the Alzheimer's Disease Neuroimaging Initiative (ADNI), a consortium that has been dedicated since the early 2000s to longitudinal studies with multi-modality brain biomarkers including MRI, FDG PET, amyloid PET and tau PET.

Other modalities continue to be studied as the techniques mature into ADNI which, according to Dr. Saykin, is in its fourth phase and has always remained dedicated to open science making all data from studies immediately publicly available.

Molecular Genetics Key to Progress

Researchers have also made progress in molecular genetics, according to Dr. Saykin, identifying three early onset genes (PSEN2, PSEN1 and APP) in the 1990s which are involved in a small but scientifically and clinically important deterministic autosomal dominant form of the disease.

The consortium Dominantly Inherited Alzheimer Network (DIAN), targets the autosomal dominant form of the disease, and research has led to the understanding that changes in biomarkers can be modeled 20 years prior to the onset of AD illness, giving clinicians a long window of therapeutic opportunity.

Dr. Saykin said that large-scale, international studies have identified 25 promising candidate genes related to multiple biological pathways that may be targeted.

Additionally, he referred to "omics" studies and the role of systems biology and bioinformatics in helping identify dysregulated networks in AD.

Research on lifestyle modifications including exercise, diet, cognitive engagement and sleep is very promising. "Protective factors have a real role to play, and large scale studies are looking at the impact of these on the brain."

Dr. Saykin said that ultimately all of this data converges and has to be put into a framework to make sense of it. He emphasized the need for supercomputing to interrogate brain, social and genetic networks and learn as much as possible.

"A broad view that puts all of these elements together is a key to having a better understanding of mechanism of the disease," he said.