Dementia

Most people have grandparents or know someone with grandparents affected by dementia which is a general term for a group of brain disorders that cause a progressive decline in cognitive abilities. 

Dementia is marked by abnormal protein deposits of 1) amyloid plaques outside neurons 2) tau tangles inside neurons that lead to brain cell death (mdpi.com). As technologies for expanding our lifespans are improving and our elderly population is growing as people are living longer, preventing and treating dementia is one of the most pressing issues of our time.

Disease-Modifying Treatments

A new generation of targeted drugs – particularly for Alzheimer's disease – is showing promise in slowing disease progression and they have taken two main approaches: 1) targeting amyloid plaque build up and 2) Targeting Tau tangles.

1) The first strategy which has taken a very different approach than those in the past, has successfully removed the amyloid plaque build up. Monoclonal antibodies are lab-engineered immune proteins that mimic the immune system's natural antibodies and are designed to seek out and neutralize the toxic proteins in the brain. These monoclonal antibody therapies have now been developed to target amyloid-β plaques. Notably, three anti-amyloid antibody drugs (including aducanumab and lecanemab) have been approved, establishing immunotherapy as a viable approach to modify Alzheimer's disease progression (mdpi.com).These antibodies help clear amyloid plaque buildup from the brain. In a clinical trial of 1,800 patients, one such drug (lecanemab) slowed the rate of cognitive decline by roughly 25% over 18 months (brightfocus.org).

2) Tau proteins (normally important for stabilizing the internal structure of neurons) can misfold and aggregate into tangles inside brain cells, contributing to cell death. There are several anti-tau drugs in development (brightfocus.org.) One study works with molecules to prevent tau from forming tangles, anti-tau antibodies to help clear toxic tau, and drugs to bolster the cell's own protein-clearance systems. Because Alzheimer's and other dementias involve multiple factors (amyloid, tau, inflammation, etc.), future treatment strategies may combine therapies – for example, pairing an anti-amyloid drug with an anti-tau drug or anti-inflammatory agent – to attack the disease on several fronts at once. (mdpi.com, mdpi.com.)

New technologies that is changing the game

CRISPR

Beyond conventional drugs, scientists are exploring cutting-edge techniques that could one day prevent or even reverse dementia. One exciting frontier is gene therapy and gene editing. A powerful gene-editing technology known as CRISPR (short for Clustered Regularly Interspaced Short Palindromic Repeats) allows researchers to precisely modify DNA, and it's now being investigated in the context of Alzheimer's disease. In 2023, researchers reported two experimental CRISPR-based strategies: one designed to mitigate the effects of the APOE-ε4 gene (the strongest genetic risk factor for Alzheimer's), and another intended to reduce production of beta-amyloid protein in the brain (aaic.alz.org.) These gene-editing approaches have proven successful and can safely reduce the harmful proteins (amyloid and tau) and have even improved memory and brain function in mouse models of Alzheimer's (aaic.alz.orgaaic.alz.org.) This exciting new technology could revolutionize the way we think about dementia prevention!

Other Promising New Approaches

Scientists are studying stem cell therapies as a way to replace or support damaged brain cells, with some early studies in animals showing improved memory and reduced brain inflammation. Novel vaccines are being designed to prompt the immune system to attack amyloid or tau proteins early in the disease. Additionally, techniques like brain stimulation (for example, using electrical or magnetic stimulation of brain networks) and advanced neurotechnology are being tested to boost cognitive function or restore lost neural connections. While these emerging therapies are largely experimental, each represents a piece of the larger puzzle.

Solving dementia is undeniably daunting but ultimately made up of smaller causes/problems. By focusing on these smaller, concrete problems, we are chipping away at the once "impossible" goal of defeating dementia. 

-------------------

If you want to learn more, here are some great sources I used for this page:

Zhang, Ling, et al.
"Alzheimer's Disease: From Molecular Pathways to Therapeutic Advances." International Journal of Molecular Sciences, vol. 26, no. 13, 2023, article 6271, MDPI, https://www.mdpi.com/1422-0067/26/13/6271.

BrightFocus Foundation.
"What Are Alzheimer's Plaques and Tangles?" BrightFocus Foundation, https://www.brightfocus.org/resource/what-are-alzheimers-plaques-and-tangles/.

Alzheimer's Association.
"CRISPR Gene Editing Shows Treatment Potential for Alzheimer's." Alzheimer's Association International Conference (AAIC) Press Release, 16 July 2023, https://aaic.alz.org/releases_2023/crispr-gene-editing-treatment-potential-alzheimers.asp.