Annals of the New York Academy of Sciences 893:154-175 (1999)
© 1999 New York Academy of Sciences

Cellular and Molecular Mechanisms Underlying Perturbed Energy Metabolism and Neuronal Degeneration in Alzheimer's and Parkinson's Diseases

MARK P. MATTSONa, WARD A. PEDERSEN, WENZHEN DUAN, CARSTEN CULMSEE AND SIMONETTA CAMANDOLA

Laboratory of Neurosciences, National Institute on Aging, Baltimore, Maryland 21224, USA


Synaptic degeneration and death of nerve cells are defining features of Alzheimer's disease (AD) and Parkinson's disease (PD), the two most prevalent age-related neurodegenerative disorders. In AD, neurons in the hippocampus and basal forebrain (brain regions that subserve learning and memory functions) are selectively vulnerable.

In PD dopamine-producing neurons in the substantia nigra-striatum (brain regions that control body movements) selectively degenerate. Studies of postmortem brain tissue from AD and PD patients have provided evidence for increased levels of oxidative stress, mitochondrial dysfunction and impaired glucose uptake in vulnerable neuronal populations.

Studies of animal and cell culture models of AD and PD suggest that increased levels of oxidative stress (membrane lipid peroxidation, in particular) may disrupt neuronal energy metabolism and ion homeostasis, by impairing the function of membrane ion-motive ATPases and glucose and glutamate transporters.

Such oxidative and metabolic compromise may thereby render neurons vulnerable to excitotoxicity and apoptosis. Studies of the pathogenic mechanisms of AD-linked mutations in amyloid precursor protein (APP) and presenilins strongly support central roles for perturbed cellular calcium homeostasis and aberrant proteolytic processing of APP as pivotal events that lead to metabolic compromise in neurons.

Specific molecular "players" in the neurodegenerative processes in AD and PD are being identified and include Par-4 and caspases (bad guys) and neurotrophic factors and stress proteins (good guys).

Interestingly, while studies continue to elucidate cellular and molecular events occurring in the brain in AD and PD, recent data suggest that both AD and PD can manifest systemic alterations in energy metabolism (e.g., increased insulin resistance and dysregulation of glucose metabolism).

Emerging evidence that dietary restriction can forestall the development of AD and PD is consistent with a major "metabolic" component to these disorders, and provides optimism that these devastating brain disorders of aging may be largely preventable.

do you get the same gluco-spike and drop with mucuna as with sinemet?

also, did you look at adrenals and spike/drop? i suspect most pwp have burned out adrenals.

My computer is dying and it looked like it had crashed yesterday, but someone came to look at it today and it's back to it's old pokey self...It's got PD too!

I have been testing my blood sugar for the last week and couldn't make a lot of sense, I will post with more detail later, I just want to give you the "jist" of the thing so you can knowq what to look for. My numbers translated into much bigger swings than everetts, but I was testing randomly at first, then got into the patterns I used when I had Gestational diabetes.... and I had a Eureka moment!!! To make a long story short, I ate a half a pkg of Saltines (also known as Soda Crackers) about 15-18 one morning while I was reading a book, all of a sudden the bottom dropped out of my meds and I took my blood sugar real quick while I could. It was 7.4 which is over the line (my range should be between 4-7) Lower is dangerous and so is higher, although your not in the coma danger zone untill about 13+. Everett has a converter link on his thread for those of you in the USA...the rest of us are on metric. My tremor went absolutley over the top and I could not move....it was serious off with sweats etc. I knew that the saltine are hi on the GI index, and I knew I needed quick intervention. I got a yellow regular sinemet into me and a clonazipam, right on top of 2 sinemet cr 25/100 and a .50 Mirapex! Lots of drugs... but I've been here before. I suspected it was the crackers turning to glucose like lightning spiking my blood sugar..but I couldn't move to test. I had to wait until the drugs kicked in about a half hour later. Then as soon as I could I tested, but I thought for sure the levels would have dropped because by now I was feeling just fine...what we call "normal" around here, as good as it gets etc. etc. etc. But I got an 11.9 reading!!!! I had probably gone higher befor I was together enough to test again because it took another 2 hours to come back to the 7 level. I suddenly understood soooo many things that had not made sense to me before. Remember (I'm sure you don't) about a year and a half ago when I had a serious meltdown an was sure I had Orthostatic tremor, because my tremor amplitude and frequency was so intense...well I got onto benzodiazapines to control it. It was very scary...and then there are all the neurologists that said...hmmmm soimething funny going on here - especially the one who saw my trmor and said "wow..has anyone else seen this?" NONE OF THEM EVEN THOUGHT ABOUT BLOOD SUGAR. I have been reading everything I've got on the Glycemic index and insulin resistance etc, and of course I have fine tuned my testing and have myself somewhat under control with regard to my fluctuations....I have learned first and foremost is that you must eat small combinatrion meals...Eating single foods like a piece of toast alone or an apple alone or a steak or whatever doesn't work. I am eating small portions of food that burns quick, medium and slow. Like make yourself a ham sandwhich with a small amt of mayo or butter, and some lettuce or have some raw veggies with. BUT cut the sandwhich into 4 quarters and eat one quarter or one half along with a carrot stick, or cucumber slices or .... and eat the rest an hour later. That will keep your blood sugar level stable...There is soo much to say here that I will have to write a small book. I'm still figuring it out. Does high blood sugar interfere with the absorption of our meds YES!!! And we all know that dyskinesia is often too much meds in thew system. Wearing off dyskinesia I'm sure is part of this. And what about the forum member who posted last year that when he picks up a fork he becomes dyskinetic!!! Yes, I've noticed that too. I could never link the clues up before... there are times when something works for us one day but not the next. Why Why Why....Unhealthy blood glucose levels can be medicated into invisibility...we think things are fine but their not. I tested randomly one day when I was feeling fine, thinking to myself "well this is a waste of a test strip"... and then tested 9!!!!! There is a major connection here. I have lots more to say but I hav't put all the pieces in place yet. Some of you this will not apply to... But I tremble to think what others are struggling with and may have even gone through DBS because the meds were just over the top, or not working. Ricks readings have been fairly moderate relative to mine, but he can detect a connection, and I think once I get my glucose reading into the safe zone consistantly, I bet I can cut back my meds. I'm not saying this is a cure, but it is a huge step towards better management. Yes Lindy, if I want to be On it's better not to eat. If you think you have a problem try this.... on an empty stomach eat a piece or two of white bread, then see what happens to your PD and if your regular dose of meds will work. If you can get a glucometer and test strips and have someone show you how to use them. Everyone has a friend with diabetes. I leave you with this little experiment and hope no one ends up in the hospital. Get a copy of "The Glucose Revolution" or a glycemic index, you want the index that bases glucose=100 not the one that uses a piece of white bread as the baseline. When is a sugar not a sugar...you'll be surprised I promise you, except for those of you who understand molecules and chains etc. I'll have lots more to say, but my computer may drop dead. This covers the essence of what I have discovered...It will take me weeks to work it all out, and I'll have to talk to a nutritionist and my Dr. and my Neuro. That alone could take months. Right now I still have lots of questions, but the answers are coming as fast as I can handle them. More as soon as I organize all my notes. I've suspected for some time that glucose levels played a role in my PD. Ricks post was the catalyst...that and 15+ SALTINES.

Hi!
I wrote this lengthy response to this thhread, then accidentally posted it in rosebud's related thread. Go here to read it:
http://forums.braintalk2.org/showthread.php?t=3132

Peggy