Autumn 2022 Newsletter

In This Issue:

• Alzheimer's Disease Biomarkers
• Drug Discovery Lab Research on ApoE4-Targeted Therapeutics for Alzheimer’s Disease Awarded Oskar Fischer Prize
• Thank You for Making a Difference!
• Clinical Trials
• Upcoming Events

The Mary S. Easton Center for Alzheimer’s Research and Care at UCLA has very active teams working on basic research, drug discovery, biomarkers for early diagnosis and clinical activity including clinical trials, cognitive testing, and patient care. 

Alzheimer’s Disease Biomarkers

By: Maryam Beigi, MD

Professor Alois Alzheimer first described Alzheimer’s disease in 1906. He called it “pre-senile dementia” as his case was in a 51-year-old female. Using a contemporary technique called silver staining, Professor Alzheimer was able to see deposits in the brain, that were later called amyloid plaques and neurofibrillary tangles (NFTs). In 1910 his coworker Emil Kraepelin further described the amyloid plaques and NFTs in brain autopsies of patients who had experienced similar symptom. At that time presence of amyloid deposits in the brains of older people was known, but NFTs were new. Professor Kraepelinnamed the disease Alzheimer’s disease in honor of Professor Alzheimer’s achievement.

In 1963 electron microscopy of NFTs in brain biopsies from two patients with advanced Alzheimer’s disease prompted more interest in the study of the disease. Since then, there has been significant progress in diagnosing the disease. Scientists have discovered that amyloid deposits are made up of the protein amyloid-beta and NFTs are composed of tau.

With invention of the CAT Scan and MRI machines, we could see volume loss in the brain, including thinning of the cortex and shrinkage of the hippocampus. This was important because, before that, we could not see these changes prior to death and brain autopsy.

Later, scientists came up with methods to measure the proteins amyloid-beta and tau in the cerebrospinal fluid (CSF) and correlate the concentration of these proteins with the diagnosis of Alzheimer’s disease. Currently, there are three validated and FDA-approved CSF biomarkers of AD: amyloid-beta 42 (Aβ42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau). CSF biomarkers are used in clinical practice to diagnose Alzheimer’s diseases with atypical presentations, and are being increasingly used in clinical trials as inclusion criteria and/or outcome measures. 

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