Dementia SOS

Colorado's Dementia News and Resource Center

Marwan Sabbagh, MD on the pathology of Alzheimer’s

Dementia SOS recently did a phone interview with Marwan Sabbagh, MD, Director of Banner Sun Health Research Institute.  Dr. Sabbagh is also the author of “The Alzheimer’s Answer.”  This first installment focuses on the pathologies of Alzheimer’s disease (beta amyloid plaques and neurofibrillary tangles).

Dementia SOS:  Plaques and tangles seem to be “the chicken and the egg” riddle of which comes first and which might be the more destructive force, or the one that sets this progressive disease in motion.   Have studies shown that beta amyloid actually kills neurons?

Marwan:  Yes, there’s clear evidence that amyloid is toxic to neurons.  The amyloid itself is toxic and then it disrupts a lot of regular, normal activity in the area, and you also get an inflammatory response to amyloid because microglia are activated – so a lot of things happen as a result of the amyloid occurring.  A lot of people [researchers] think that tau tangles are a response to the amyloid, and those tangles are toxic to neurons as well.

Dementia SOS:  OK, so tau tangles generally follow the accumulation of beta amyloid?

Marwan:  That’s not always agreed upon, but I think there’s a majority of agreement that tangles follow amyloid.

Dementia SOS:  There are some drug treatments being designed to prevent the initial accumulation of amyloid.  Can you describe some of these?

Marwan:  I would call them amyloid-based immunotherapy drugs.  We have them in basically what you would call DM’s, or Disease Modifying, and then you have the symptomatic treatments that are still being developed.  The DM’s are mostly centered on amyloid – either to inhibit production of amyloid or enhance clearance of amyloid.  The immunotherapy drugs are for enhancement of clearance.

Dementia SOS:  So in your opinion, inhibiting amyloid accumulation might prevent the spreading of the Alzheimer pathology?

Marwan:  I wouldn’t agree with that necessarily.  I consider kind of taking a “20,000 foot view” of the disease.  Alzheimer’s is a bi-phasic disease: the pre-symptomatic amyloid phase and the symptomatic phase which involves tangled tau, excitatory neuro-toxicity chemical breakdown [hyper-phosphorylated tau protein].

The reason I tell you that is that clearing out amyloid once it is present and symptomatic may not be the best approach at the time.  There’s clear evidence that once you have symptomatic Alzheimer’s disease, your amyloid does not necessarily change as you get more demented.  It actually stays pretty fixed and static.

So the question is “are we treating with amyloid based approaches too late?”  The reason we are going after amyloid is that we know it is a critical part of the disease and it’s an easy target to go after, but it’s not inside the neurons themselves.

Dementia SOS:  OK.  So, at the point when the disease has spread inside the neurons and corrupted cells, do you feel like there is a way to treat that?

Marwan:  Well, it turns out that going after tau has been a tricky business.  There have been three attempts at this: lithium, valproate and methylene blue tau rx products [aka tau aggregation inhibitors] that were reported in 2008.

Dementia SOS:  Are there other proteins besides tau that become corrupted within neurons, or other processes involved in brain cell destruction?

Marwan:  One other protein that researchers tried to look at with amyloid, glycocyamine and GlyCAM, is associated with proteins of aggregation of amyloid.  The conventional wisdom is that if you block those proteins you will reduce the aggregation of amyloid so that has been looked at as an approach…gene therapy has been looked at as an approach…anti-inflammatories have been looked at…stimulating a bunch of receptors – there are all kinds of different things that have been looked at.

Dementia SOS:  With the brain bank studies at Banner Sun Health Research, the hippocampus and posteriomedial cortex are areas of the brain that have been shown to be severely compromised by AD early on – is it possible that those areas are triggers for the progression of AD?

Marwan:  Absolutely.  The hippocampus is the seat of short term memory and so when people are forgetful and they repeat themselves it’s because their hippocampus is damaged and compromised.  We think, especially if you go back to the Brock stage system for almost 20 years, that tangles form first in the hippocampus and the entorhinal cortex.  So that is the beginning stage of where the injury occurs.

Dementia SOS:  Are there any medications out there being researched to try to specifically protect the hippocampus?

Marwan:  The answer is, as far as I know, “no.”  The hippocampus is a very delicate part of the brain.  It has a lot of cholinergic aspects so the concept is that if you give them acetylcholine enhancement inhibitors you are improving some of the hippocampal function.  But there are no targeted, specific drugs being developed for the hippocampus that I know of.

Follow this link for  further discussion with Marwan Sabbagh, MD on the topic of Alzheimer’s prevention.

January 25, 2012 - Posted by | Alzheimer's Disease, Brain Cells, Interviews, Medications, The Human Brain | , , , , , , , , ,

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