Neuro Review Article of Alzheimer’s disease
ALZHEIMER’S DISEASE AND INFLAMMATION: A REVIEW OF CELLULAR AND THERAPEUTIC
MECHANISMS
Alzheimer’s
disease is the fourth leading cause of death in persons over the age of
65. It is incurable and progressive and
affects millions of people across the world.
Alzheimer’s disease (AD) is the most common neurodegenerative disease
that causes dementia. The three major
pathological hallmarks of this disease are characterized as senile plaques,
neurofibrillary tangles, and inflammation.
Senile plaques consist primarily of protein deposits, namely b-amyloid
fragments. These amyloid fragments seem
to mediate inflammatory mechanisms by activating microglial cells via the
complement pathway in a similar fashion to immunoglobulins. Platelets are a major source of amyloid
fragments thus therapies are proposed to curve platelet numbers and thus a
source of protein fragments. Also the
use of NSAIDS to reduce the inflammatory microglial cell activation is
discussed.
Inflammation
of neuronal tissue can both be beneficial and detrimental depending on
circumstances. For example in brain
injury the inflammatory response can:
aid in clearing out dead cells, debris, inhibit neuro toxic cytokines,
and promote growth factors needed for recovery. Conversely improper or chronic inflammation can cause severe
damage and widespread death of neuronal cells worsening prognosis. Possible drug interventions to curve these
deleterious effects are proposed.
Evidence from RA patients who consume anti-inflammatory medications
regularly does seem to show slowing of the progression of AD. In conclusion the author’s call for future
studies aimed at targeting the inflammatory process via NSAIDS and
anti-platelet therapies.
Source: Glenda
Halliday,* Stephen R Robinson,‡ Claire Shepherd* and Jillian Kril. BRIEF
REVIEW: ALZHEIMER’S DISEASE AND INFLAMMATION: A REVIEW OF CELLULAR AND
THERAPEUTIC MECHANISMS, Clinical
and Experimental Pharmacology and Physiology (2000) 27, 1–8.
This is a really interesting concept, but definitely carries some of those risk/benefit stipulations we have been talking about this semester. Like you mentioned Mike, the people who have the reduced progression of AD are already using NSAIDs on a regular basis to manage their rheumatoid arthritis. What I really end up wondering is how often and how early on would a person have to start taking anti-inflammatory medication in order to slow the disease, especially when considering the downsides to NSAIDs. Like we talked about in class, using this medication comes with an increased cardiovascular risk. I think it would be really cool to see a specific study of the effects of NSAID use on the pathology and physiological development of AD.
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