Liver Function and Alzheimer's Disease

Peripheral reduction of β-amyloid is sufficient to reduce brain β-amyloid: implications for Alzheimer's disease.
Sutcliffe JG, Hedlund PB, Thomas EA, Bloom FE, Hilbush BS. (2011)

"We show that the activity of mouse Psen2, as measured by levels of mRNA accumulation, unexpectedly is heritable in the liver but not the brain, suggesting liver as the origin of brain Aβ deposits. Administration of STI571, a cancer therapeutic that does not cross the blood-brain barrier, reduced accumulation of Aβ in both the blood and the brain, confirming brain Aβ's peripheral origin and suggesting that STI571 and related compounds might have therapeutic/prophylactic value in human Alzheimer's disease."


Peripheral Amyloid-β Levels Regulate Amyloid-β Clearance from the Central Nervous System
Marcos A. Marques,abc1 J. Jacob Kulstad,abd1 Christopher E. Savard,be Pattie S. Green,be Sum P. Lee,be Suzanne Craft,abc G. Stennis Watson,abc and David G. Cookabef (2009)

"These data also support and extend previous findings by illustrating the substantial contribution of the liver to peripheral Aβ clearance. To the extent the peripheral circulatory system can act as an Aβ sink, these data demonstrate that the liver is the primary drain."

Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer's disease.
Astarita G, Jung KM, Berchtold NC, Nguyen VQ, Gillen DL, Head E, Cotman CW, Piomelli D.
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America. (2010)

"Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease...The results indicate that a deficit in d-bifunctional protein activity impairs docosahexaenoic acid biosynthesis in liver of Alzheimer's disease patients, lessening the flux of this neuroprotective fatty acid to the brain."

Silymarin attenuated the amyloid β plaque burden and improved behavioral abnormalities in an Alzheimer's disease mouse model.
Murata N, Murakami K, Ozawa Y, Kinoshita N, Irie K, Shirasawa T, Shimizu T.
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. (2010)

"In vivo studies had indicated a significant reduction in brain Aβ deposition and improvement in behavioral abnormalities in amyloid precursor protein (APP) transgenic mice that had been preventively treated with a powdered diet containing 0.1% silymarin for 6 months. The silymarin-treated APP mice also showed less anxiety than the vehicle-treated APP mice."


Fatty liver disease can mimic symptoms of Alzheimer's Disease
By Roz Zurko on 2011-06-18

"The doctors explained that Wilson's memory lapses and erratic behavior was due to liver disease. "When you think about this kind of thing, you think about dementia or Alzheimer's," Patricia says. "You don't think about the liver," which is most likely what any average person would be thinking under the circumstances.

The diagnosis was cirrhosis of the liver, just like alcoholics get, but Wilson's disease was not from alcohol, it was caused by fat that was deposited in his liver over the years. He is overweight and too much fat in his liver eventually caused it to malfunction. This is not an isolated incident by any means."


Heme Oxygenase: A Font of Multiple Messengers
Solomon H Snyder MD and David E Baranano
The Johns Hopkins University, School of Medicine, Departments of Neuroscience, Pharmacology and Molecular Sciences, and Psychiatry, Baltimore, MD USA

"We have recently obtained direct evidence for a neuroprotective role of HO2 linked to Alzheimer's disease (Takahashi et al. 2000). Yeast 2-hybrid and other protein-binding studies reveal HO2 and HO1 binding to the amyloid precursor protein (APP). This interaction has no effect on APP processing but does result in inhibition of HO activity. The APP derivatives that occur in familial forms of Alzheimer's disease are much more potent than normal APP in inhibiting HO activity. To examine in vivo consequences of this finding, we utilized mice with the "Swedish" mutant APP. HO2 activity in cerebral cortical cultures from these mice is markedly reduced as is evident by profoundly diminished staining for bilirubin. Moreover, neurotoxicity elicited by hemin or hydrogen peroxide is markedly increased in cultures from Swedish mutant brain. While the HO inhibitor tin protoporphyrin IX worsens neurotoxicity in control cultures, it is ineffective in Swedish cultures in which NO activity is already diminished. We presume that the loss of physiologic protection by bilirubin in brains of patients with familial Alzheimer's disease increases sensitivity to the neurotoxic effects of the high levels of amyloid beta peptide generated in these patients."

Decreased plasma antioxidants in patients with Alzheimer's disease.
Kim TS, Pae CU, Yoon SJ, Jang WY, Lee NJ, Kim JJ, Lee SJ, Lee C, Paik IH, Lee CU.
Department of Psychiatry, Kangnam St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Seoul, Korea. (2006)

"A significant reduction in the albumin, bilirubin, and uric acid levels in the AD group was found compared to those of the control group... This study showed that oxidative injuries could be involved in the pathogenesis of AD."


Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease.
Neurology. 2001 Oct 23;57(8):1515-7.
Adair JC, Knoefel JE, Morgan N.
Neurology Service, Albuquerque Veterans Affairs Medical Center, New Mexico, USA.

"Comparison of interval change favored NAC treatment on nearly every outcome measure, although significant differences were obtained only for a subset of cognitive tasks."

Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis.
Hager K, Kenklies M, McAfoose J, Engel J, Münch G.
Department of Medical Rehabilitation and Geriatrics, Henriettenstiftung, Hannover, Germany. (2007)

"The treatment led to a stabilization of cognitive functions in the study group, demonstrated by constant scores in two neuropsychological tests (the mini mental state exam, MMSE and the Alzheimer's disease assessment score cognitive subscale, ADAScog)... our data suggest that treatment with alpha-lipoic acid might be a successful 'neuroprotective' therapy option for AD."