Research from the Laboratory of Psychiatry and Experimental Alzheimers Research (http://www2.i-med.ac.at/psychlab/) at the Medical University Innsbruck (Austria) demonstrated that chronic high fat cholesterol diet in rats exhibited pathologies similar to Alzheimer’s disease. The results were published in Molecular Cellular Neuroscience (45(4):408-417, 2010) with lead author Dr. Christian Humpel. The study was co-authored by PhD students, Celine Ullrich and Michael Pirchl, from the same Laboratory.
Alzheimer’s disease is a severe neurodegenerative disorder of the brain that is characterized by loss of memory and cognitive decline. The majority of Alzheimer’s disease cases are sporadic (risk age >60 years), and only <2.5% have a genetic disposition. It is estimated that in 2050, approximately 80 million people will suffer from Alzheimer's disease worldwide. The major pathological hallmarks of Alzheimer's disease are extracellular aggregates (plaques) of the small peptide beta-amyloid, hyperphosphorylation of the protein tau and subsequent formation of intracellular neurofibrillary tangles, degeneration of neurons secreting the neurotransmitter acetylcholine, inflammation, and cerebrovascular dysfunction.
The causes for Alzheimer’s disease are not known, but dysregulation of amyloid-precursor protein expression and beta-amyloid clearance is hypothesized (beta-amyloid cascade). Alternatively, a pathological cascade of events may trigger hyper-phosphorylation of tau, putting the tau-hypothesis into the center.
A third hypothesis suggests that chronic long-lasting mild cerebrovascular damage, including inflammatory processes and oxidative stress, may cause Alzheimer’s disease. It has been suggested that Alzheimer’s disease starts 20-30 years before first symptoms appear and recent studies have shown, that high cholesterol levels are linked to the pathology of this disease.
The aim of the study led by Humpel was to study the effects of hypercholesterolemia in adult rats. Male 6 months old Sprague Dawley rats were fed with normal food (controls) or with a special 5% cholesterol-enriched diet (hypercholesterolemia). After 5 months animals were tested for behavioral impairments and pathological markers similar to those found in the brains of patients with Alzheimer’s disease. The results showed that chronic hypercholesterolemia caused memory impairment, cholinergic dysfunction, inflammation, enhanced cortical beta-amyloid and tau and induced microbleedings, all indications, which resemble an Alzheimer’s disease-like pathology.
Thus the data are in line with earlier studies showing that high fat lipids, including cholesterol, may participate in the development of sporadic Alzheimer’s disease. However, since Alzheimer’s disease is a complex heterogenous disease, these data do not allow the conclusion that cholesterol alone is responsible for the disease. It can be speculated that chronic mild cerebrovascular damage caused and potentiated by different vascular risk factors (including cholesterol) may contribute to these pathologies. It needs to be determined in future studies how mild chronic microvascular bleedings, silent strokes and mild blood-brain barrier damage over decades may play a role in the development of this disease. Indeed several data (Ladecola, Nat.Rev.Neurosci. 5, 347-360, 2004) support the view that Alzheimer’s disease can be considered as a vascular disease and that a dysfunctional clearance of beta-amyloid from brain to blood and vice versa may be a secondary important step in the cascade of initiation of the disease.
This study was supported by the Austrian Science Funds (P19122-B05). Additional details are available in the full publication: http:dx.doi.org/10.1016/j.mcn.2010.08.001
About Molecular and Cellular Neuroscience
Molecular and Cellular Neuroscience publishes original research of exceptional significance from those areas of the neurosciences indicated by the broadest interpretation of the journal’s title. In particular, the journal focuses on synaptic maintenance and organization, neuron-glia communication and regenerative neurobiology. As part of the submission process, authors are asked to state why they consider their paper is of such significance.
Furthermore, since rapid peer-review and publication of such research is of paramount importance, extended cycles of article revision and re-review will not be entered into; it is anticipated that authors will fully address all referees’ comments during the course of a single revision of their original manuscript.
Elsevier is a world-leading publisher of scientific, technical and medical information products and services. The company works in partnership with the global science and health communities to publish more than 2,000 journals, including the Lancet (http://www.thelancet.com) and Cell (http://www.cell.com), and close to 20,000 book titles, including major reference works from Mosby and Saunders. Elsevier’s online solutions include ScienceDirect (http://www.sciencedirect.com), Scopus (http://www.scopus.com), Reaxys (http://www.reaxys.com), MD Consult (http://www.mdconsult.com) and Nursing Consult (http://www.nursingconsult.com), which enhance the productivity of science and health professionals, and the SciVal suite (http://www.scival.com) and MEDai’s Pinpoint Review (http://www.medai.com), which help research and health care institutions deliver better outcomes more cost-effectively.
Contact: Christian Humpel
A global business headquartered in Amsterdam, Elsevier (http://www.elsevier.com) employs 7,000 people worldwide. The company is part of Reed Elsevier Group PLC (http://www.reedelsevier.com), a world-leading publisher and information provider. The ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).