Alzheimer’s Disease as an Epigenetic Disease with Dr. David Katz

Alzheimer’s disease is a devastating neurodegenerative condition that slowly erodes memory, cognitive function, and the ability to perform even the simplest tasks. It’s heartbreaking not only for those diagnosed but also for their loved ones as they watch a gradual loss of the person they knew. This is exactly how I felt in 2015 when I watched my grandmother be taken by this awful disease.

The disease progresses as abnormal protein deposits (amyloid plaques and tau tangles) damage brain cells, leading to widespread brain shrinkage. Despite ongoing research, effective treatments remain limited, making Alzheimer’s one of the most challenging and impactful diseases today. However, new research is uncovering fresh perspectives on its underlying causes. One emerging view is that beyond the traditional focus on protein deposits, epigenetic changes might play a crucial role in driving the disease.

In this week’s episode of the Everything Epigenetics podcast, Dr. Katz and I focus on his labs surprising journey that led them to believe that Alzheimer’s disease is an epigenetic disease resulting from a loss of cell fate. Dr. Katz anticipates that his lab’s work will advance drug discovery through epigenetics. If no other company exploits the work, his will, even though it currently exists only on paper. “Most of the epigenetic drugs are cancer therapies,” he notes. “More recently, drugs that target epigenetic enzymes have been pursued for a wide range of diseases, ranging from muscular dystrophies to Alzheimer’s disease. Going forward, it will be exciting to see if epigenetic-based therapies prove to be effective against other diseases.”

You’ll learn about:

• Dr. Katz's interest in the development of the germline of the roundworm Caenorhabditis elegans
• Histone methylation and how this mechanism influences cell fate, as well as how this mechanism can go awry
• Neuroepigenetic mechanisms in disease
• Novel functions for epigenetics in the fields of Rett syndrome, Fragile X syndrome, and Alzheimer's disease research
• How the above discoveries underscore the vital importance of epigenetics in human neurological disorders
• The first identified histone demethylase, lysine-specific demethylase 1 (LSD1)
• Why LSD1 is important 
• What it means that LSD1 is required in the germ line to reprogram histone H3K4 methylation
• How this pathway prevents epigenetic transcriptional memory from being inherited transgenerationally
• How this work can advance drug discovery in Alzheimer's disease 
• CURE  (a program that Dr. Katz established with a nearby liberal arts college, Oglethorpe)
• How CURE promotes DEI in science

Chapters:
00:00 Introduction to Epigenetics
07:50 Hannah’s Insights on Recent Research
15:55 David’s Perspective on Practical Applications
25:18 The Impact of Lifestyle on Epigen