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Mind your ApoA1 levels!

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
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Julie G
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Mind your ApoA1 levels!

Postby Julie G » Thu Jan 05, 2017 4:12 pm

This new paper adds to a growing body of evidence that reduced HDL/ApoA1 may predict conversion to AD for E4 carriers. Conversely, higher levels appear to be protective. The good news; for many, this biomarker is amenable to diet/lifestyle interventions.

Apolipoprotein A1 in Cerebrospinal Fluid and Plasma and Progression to Alzheimer’s Disease in Non-Demented Elderly
https://www.ncbi.nlm.nih.gov/pubmed/28035918
Abstract: Background: HDL-cholesterol transporter Apolipoprotein A1 (ApoA1) holds neuroprotective properties, such as inhibition of amyloid-β aggregation. Low plasma ApoA1 concentrations are associated with Alzheimer’s disease (AD). Little is known about ApoA1 levels in the pre-dementia stages of AD. Objective: To investigate associations between cerebrospinal fluid (CSF) and plasma ApoA1 levels and clinical progression toward AD in non-demented elderly. Methods: From the Amsterdam Dementia Cohort, we included 429 non-demented elderly with subjective cognitive decline (SCD; n = 206, 61±9 years, Mini-Mental State Exam (MMSE) 28±2) and mild cognitive impairment (MCI; n = 223, 67±8 years, MMSE 27±2), with a mean follow-up of 2.5±1.6 years. We used Cox proportional hazard models to investigate relations between CSF and plasma ApoA1 concentrations and clinical progression, defined as progression to MCI or AD for SCD, and progression to AD for MCI. Analyses were adjusted for age, gender, MMSE, and plasma cholesterol levels. Analyses were stratified for diagnosis and APOE ɛ4 carriership. Results: 117 patients (27%) showed clinical progression. One standard deviation increase of CSF ApoA1 was associated with a 30% increased risk of clinical progression (hazard ratio (HR) (95% CI)  = 1.3(1.0–1.6)). The effect appeared to be attributable to the APOE ɛ4 carriers with SCD (HR 3.3(1.0–10.9)). Lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOE ɛ4 carriers with SCD (HR 5.0(1.3–18.9)). Conclusion: Higher CSF and lower plasma ApoA1 levels were associated with an increased risk of clinical progression in APOE ɛ4 carriers with SCD; suggesting that ApoA1 may be involved in the earliest stages of AD.

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Re: Mind your ApoA1 levels!

Postby LG1 » Thu Jan 05, 2017 7:38 pm

Juliegee wrote:This new paper adds to a growing body of evidence that reduced HDL/ApoA1 may predict conversion to AD for E4 carriers. Conversely, higher levels appear to be protective. The good news; for many, this biomarker is amenable to diet/lifestyle interventions.

Apolipoprotein A1 in Cerebrospinal Fluid and Plasma and Progression to Alzheimer’s Disease in Non-Demented Elderly
https://www.ncbi.nlm.nih.gov/pubmed/28035918

Julie, do you know what they mean by "One standard deviation increase"?

This one I hit out of the park. 178 ApoA1, .66 ratio. I found some markers in Promethease pointing to higher HDL. Hope it ends up being relevant.

As for raising HDL, here is a little interesting info. I used to drink chardonnay in the evenings. My HDL tested at 136 during this time. I quit alcohol except for an occasional glass of champagne or prosecco. Now my HDL is 100. Quite a drop but still great.

Of course, it is of no consequence to anyone since we aren't suppose to be drinking... but maybe there is a way to get the effects without the alcohol? Reservatol - but that's red wine. Not sure why my white had that affect. Maybe it wasn't the wine but something I'm not remembering.
ε4/ε4

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Re: Mind your ApoA1 levels!

Postby marty » Fri Jan 06, 2017 8:07 am

This is another piece in a large puzzle. I wonder what it means.

My initial reaction is to think about the association of higher HDL with protection against heart disease. That association begged the question as to whether increasing HDL in patients prevents heart disease. So far, the major studies that did raise HDL did not appear beneficial. That took a massive amount of money to investigate. Further, there was a large market for supplements promising heart health to millions of buyers.

It's hard to do nothing, and I'm in the same boat as everyone here. I wish we knew the answers today.

http://circres.ahajournals.org/content/118/4/732.short

Trials of niacin added to statin have failed to demonstrate cardiac benefits, and 3 cholesterol ester transfer protein inhibitors have also failed to reduce atherosclerotic cardiovascular disease risk, despite producing substantial increases in HDL levels.

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Re: Mind your ApoA1 levels!

Postby slacker » Fri Jan 06, 2017 10:10 am

marty wrote:
...Trials of niacin added to statin have failed to demonstrate cardiac benefits...


I wonder if niacin showed cardiac benefit in those with elevated Lp(a) or presence of ApoE4? Was the study powered to evaluate this?
Slacker
E4/E4

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Julie G
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Re: Mind your ApoA1 levels!

Postby Julie G » Fri Jan 06, 2017 11:32 am

Marty, many of us are following the cardiovascular angle too. So far, it looks though pharmaceutically induced higher HDL levels are of little to no value. Looks like HDL has to be earned the old fashioned way. The relationship between HDL and neurodegeneration is pretty solid. (See paper below.) I’m unaware, however, of anyone studying it from a pharmaceutically induced angle.

HDL and cholesterol handling in the brain.
https://www.ncbi.nlm.nih.gov/pubmed/24907980

ApoA1 isn’t created in the CNS, but rather crosses the from the periphery. Both higher CNS and peripheral levels offer neuroprotection. We know that ApoA1 is closely tied to APOE levels with E4 carriers having the lowest levels; E4<E3<E2. In this recent paper, Dr. Mahley hypothesizes that higher APOE levels might even be detrimental In E4 carriers because of the protein fragmentation.

Central Nervous System Lipoproteins
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942259/

Ah, but not so fast! This contradicts Dr. Rasmussen's work (below) indicating that higher APOE levels (regardless of genotype; i.e. including E4) protected against AD in humans. In short, any dietary/lifestyle approach that leads to lower HDL/ApoA1/APOE levels may be less than optimal for E4 carriers.
It's hard to do nothing, and I'm in the same boat as everyone here. I wish we knew the answers today.

Until we have effective Pharma, we can eat avocados & exercise.

Plasma levels of apolipoprotein E and risk of dementia in the general population.
https://www.ncbi.nlm.nih.gov/pubmed/25469919
Low plasma levels of apoE are associated with increased risk of future Alzheimer disease and all dementia in the general population, independent of ε2/ε3/ε4 APOE genotype. This is clinically relevant, because no plasma biomarkers are currently implemented. Hence, plasma levels of apoE may be a new, easily accessible preclinical biomarker.

LG1, congrats on your enviably high levels. I’ll let our statisticians answer your question, LOL. I’m hooked up to an IVIG drip and feeling pretty loopy from pre-meds. Apologies if I’m not making sense ;)

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Re: Mind your ApoA1 levels!

Postby Thx4thegenes » Fri Jan 06, 2017 12:40 pm

Lol, Juliegee, you are making sense. I was just thinking how intelligent you are as well as many others here on this site! Talk about dedication to the forum, being hooked up and everything! Wow. Hope all is well. :)

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Re: Mind your ApoA1 levels!

Postby marty » Fri Jan 06, 2017 3:01 pm

[quote="Juliegee"]Marty, many of us are following the cardiovascular angle too. So far, it looks though pharmaceutically induced higher HDL levels are of little to no value. For now, looks like HDL has to be earned the old fashioned way. The relationship between HDL and neurodegeneration is pretty solid. I’m unaware, however, of anyone studying it from a pharmaceutically induced angle with regards to nueroprotection.

HDL and cholesterol handling in the brain.
https://www.ncbi.nlm.nih.gov/pubmed/24907980

Juliegee, I always appreciate your writing.

We are all doing the best we can with only small parts of the puzzle.

Avocados make sense at this point. And hey, they taste good, too. Being from the midwest, they aren't as cheap as in some areas, but I have one most days.

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Re: Mind your ApoA1 levels!

Postby Julie G » Fri Jan 06, 2017 3:19 pm

We are all doing the best we can with only small parts of the puzzle.

Amen!

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Re: Mind your ApoA1 levels!

Postby circular » Fri Jan 06, 2017 10:23 pm

I'm all confused and out of what little spare brain power I've had for these intersting forum topics. What does this mean, if anyone has a take ... My last HDL was 62 and my last APO A-1 was 142.
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Mind your ApoA1 levels!

Postby Hepoberman » Sat Jan 07, 2017 3:04 am

Circ, think of it this way: You have 142 garbage trucks (lipoproteins) and they have 62 yards (cholesterol) of garbage in them.

I've heard it explained like this, "LDL are delivery trucks, HDL are garbage trucks." As you might imagine, all delivery trucks and no garbage trucks makes for a very messy neighborhood. We need the garbage cleared and ApoA1 does that job.

So while it is usually a good sign to see someone has plenty of garbage trucks at work, it is also worth asking, "Why are all those garbage trucks so full?" We can't really learn much from an individuals APOA1 levels alone because there are too many distortions possible.

If we don't have as much garbage to remove, we will have lower HDL. This is actually a sign of good health and requires a more nuanced understand of cholesterol metabolism than just thinking, "High HDL is good". -Not necessarily!


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