Discovery of Alzheimer’s Disease Variants

Alzheimer’s disease (AD) is a disorder that causes degeneration of the cells in the brain and it is the main cause of dementia or loss of memory, which is characterized by a decline in thinking and independence in personal daily activities.

There are 10.7% or 6.5 million Americans (65 and over) living with Alzheimer’s in 2022. Every 65 seconds, one person in the US develops Alzheimer’s disease. The number of individuals living with Alzheimer’s disease is projected to increase to 13.8 million by 2060. 72.9% (4.72 million) of the total Alzheimer’s cases in the US are people aged 75 and above. 

Senile plaques (aggregates of a protein called amyloid outside of cells) and neurofibrillary (nerve cell) changes are regarded as neuropathological hallmarks of Alzhemer’s disease. With age, the brain shrinks, which makes brain fluid collection areas known as ventricles appear larger.

AD is classified in stages of progression: 1) pre-clinical stage, 2) early stage, 3) moderate stage, and 4) severe or late-stage. 

Recently, scientists have discovered five new biological variants of AD through cerebrospinal fluid (brain fluid) analysis. These forms differ in blood-brain barrier integrity, amyloid production, nerve cell growth, immune system functioning, and protein synthesis. 

The study authors researched 1058 proteins in the cerebrospinal fluid (brain fluid) of 419 people with AD. The first variation found, called subtype 1, is distinguished by increased amyloid aggregates collection and increased cerebrospinal fluid (brain fluid- CSF) levels. In subtype 2, there is a disruption of the blood-brain barrier, a decrease in the synthesis of amyloid, and a reduction in the growth/division of nerve cells. Subtype 3 has increased CSF and decreased protein levels. In subtype 4 there is choroid plexus (a network of blood vessels in each ventricle of the brain) malfunction and decreased amyloid metabolism. Subtype 5 is associated with blood-brain barrier dysfunction and leaking of proteins into the brain.

The discovery of these subtypes has significant implications for medication research and development. Drugs that block the production of amyloid, for instance, may be effective where amyloid production is higher (subtype 1) but detrimental in the variant where amyloid production is lower (subtypes 2 and 4).

Different treatments may be required for different forms of AD. The results presented here may also explain why previously tested drugs have been ineffective or minimally effective for some patients but work well for others. Given the discovery of these new subtypes of AD, more research is necessary to further characterize the variants to provide individualized and appropriate care to patients.

Written by Fatema Tasnim

Edited by Caroline Cencer PhD

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