Learning from Down Syndrome: Understanding Connection with AD ~ Domenico Pratico, MD, FCPP

Down’s syndrome (DS), the most common genetic disability worldwide, offers a unique insight into Alzheimer’s disease due to a shared genetic link. This article explores the intriguing connection between these two conditions and the potential it hold for advancing our understanding of Alzheimer’s disease.
Learning from Down Syndrome
Down’s Syndrome and Alzheimer’s
In 1866, Dr. John Langdon Down described DS, characterized by an extra chromosome 21, or “Trisomy 21.” Nearly four decades ago, researchers established a link between DS and Alzheimer’s disease. Individuals with DS develop amyloid beta plaques and tau neurofibrillary tangles in their brains by the age of 40, mirroring Alzheimer’s pathology.

Genetic Link: Chromosome 21 and Amyloid Beta
Chromosome 21 harbors the gene responsible for amyloid beta protein production, a key component of amyloid plaques. With three copies of this gene, individuals with DS produce excess amyloid beta proteins from an early age, resulting in amyloid plaque deposition, even in infants with DS. This accelerated brain aging in DS provides a unique window into the early mechanisms of Alzheimer’s disease.

Early Brain Abnormalities: Precursor to Alzheimer’s
In young adults with DS, amyloid beta plaques initially accumulate in brain regions responsible for emotional reactions, executive functions, and memory processes. Though seemingly “normal” at this stage, cells in these regions already exhibit characteristics that lead to “cell suicide” or apoptosis later in life.

Cognitive Deficits and Morphological Anomalies
DS is accompanied by various medical and physical manifestations, including congenital heart diseases and skeletal abnormalities. Cognitive deficits in DS are linked to morphological brain abnormalities, some directly influenced by elevated amyloid beta protein levels. These abnormalities impact the architecture of brain cells, resulting in a reduced number and altered shape of dendritic spines, crucial for learning and memory. Strikingly, similar findings are observed in Alzheimer’s disease.

Our Research
Our lab’s ongoing research focuses on deciphering the mechanisms behind dendritic spine abnormalities, cognitive impairments, synaptic dysfunctions, and related areas of investigation. This exploration holds the potential to deepen our understanding of both DS and Alzheimer’s disease.

I firmly believe that the early emergence of Alzheimer’s disease-like abnormalities in the brains of individuals with DS underscores the growing imperative for early interventions to halt disease progression. Furthermore, it holds the potential to provide valuable insights for the prevention and treatment of Alzheimer’s disease as well.

If you like this blog post, I also wrote about – Is Alzheimer’s the most expensive disease in the country? – Domenico Pratico

Domenico Praticò, MD, is the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research, Professor and Director of the Alzheimer’s Center at Temple, and Professor of Pharmacology at the Lewis Katz School of Medicine at Temple University

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