Low cholesterol levels associated with Alzheimer's disease

This study was published in Collegium Antropologicum 2011 Jan;35 Suppl 1:115-20

Study title and authors:
Serum lipid levels in patients with Alzheimer's disease.

Presećki P, Mück-Seler D, Mimica N, Pivac N, Mustapić M, Stipcević T, Smalc VF.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/21648320

The mini–mental state examination (MMSE) is a 30-point questionnaire that is used for the diagnosis of Alzheimer's Disease. Any score greater than or equal to 27 points (out of 30) indicates normal cognition. Scores between 10-19 indicate the presence of Alzheimer's disease and scores of nine or less indicate severe Alzheimer's disease.

The aim of this study was to determine the relationship of cholesterol levels with Alzheimer's disease. The study included 50 women, aged 56-96 years, who had their cholesterol levels compared with 58 age matched healthy women. Patients with Alzheimer's disease were subdivided into two groups of 19 patients in the middle (MMSE 10-19) and 31 patients in the severe late (MMSE 0-9) phase of Alzheimer's disease.

The study found:
(a) Total cholesterol levels were significantly lower in all patients with Alzheimer's disease than in healthy subjects.
(b) Patients in the severe late stage of Alzheimer's disease had significantly lower total cholesterol, HDL Cholesterol, LDL Cholesterol and Triglyceride levels than healthy subjects.
(c) Patients in the severe late stage of Alzheimer's disease had significantly lower cholesterol and LDL Cholesterol levels than patients in the middle stage of Alzheimer's disease.

Presećki concluded: "Lipid (cholesterol) levels are reduced in female patients with Alzheimer's disease compared to lipid values in elderly female healthy controls ...and serum lipid levels are the lowest in patients in the late stage of Alzheimer's disease."

Links to other studies:
Alzheimer’s patients have significantly reduced levels of cholesterol and fats in the brain
High cholesterol levels associated with a decreased risk of Alzheimers disease
Low cholesterol levels are associated with a higher risk of Alzheimer's

Low cholesterol levels may be associated with the development of dementia

This study was published in the Archives of Neurology 2007 Jan;64(1):103-7

Study title and authors:
Twenty-six-year change in total cholesterol levels and incident dementia: the Honolulu-Asia Aging Study.

Stewart R, White LR, Xue QL, Launer LJ.
King's College London (Institute of Psychiatry), Section of Epidemiology, England. r.stewart@iop.kcl.ac.uk

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17210816

This study investigated the relationship between cholesterol levels and the risk of dementia. The study included 1,027 men who were followed for 26 years. Over the course of the study the men had their cholesterol levels measured on five occasions and were screened for dementia on two occasions.

The study found that  cholesterol levels in men with dementia and, in particular, those with Alzheimer disease had declined at least 15 years before the diagnosis and remained lower than cholesterol levels in men without dementia throughout that period.

Stewart concluded: "A decline in serum total cholesterol levels may be associated with early stages in the development of dementia".

Higher levels of cholesterol are associated with a decreased risk of Alzheimer's Disease

This study was published in the Archives of Neurology 2004 May;61(5):705-14

Study title and authors:
Relation of plasma lipids to Alzheimer disease and vascular dementia.

Reitz C, Tang MX, Luchsinger J, Mayeux R.
Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, NY, USA.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/15148148

This study investigated the relationship between cholesterol levels and Alzheimer disease and vascular dementia. (Vascular dementia is caused by problems in the supply of blood to the brain usually from a stroke). The study included 4,316 participants aged 65 years and older.

The study found:
(a) The risk of prevalent Alzheimer's was 28% higher in those who had low cholesterol, under 172 mg/gL (4.4 mmol/L), compared to those with cholesterol levels between 197-225 mg/dL (5.1-5.8 mmol/L).
(b) The risk of prevalent Alzheimer's was 34% higher in those who had low levels of high density lipoprotein (HDL) cholesterol, under 37 mg/gL (.95 mmol/L), compared to those with high density lipoprotein (HDL) cholesterol levels over 55 mg/dL (1.4 mmol/L).
(c) The risk of prevalent vascular dementia was 20% higher in those who had low cholesterol, under 172 mg/gL (4.4 mmol/L), compared to those with cholesterol levels between 197-225 mg/dL (5.1-5.8 mmol/L).
(d) The risk of prevalent vascular dementia was 40% higher in those who had low levels of high density lipoprotein (HDL) cholesterol, under 37 mg/gL (.95 mmol/L), compared to those with high density lipoprotein (HDL) cholesterol levels over 55 mg/dL (1.4 mmol/L).

The lead author of the study Dr Christiane Reitz commented: "Our results do not support the hypothesis that the risk of Alzheimer's Disease is associated with plasma lipid levels. They also do not support the hypothesis that statin use is associated with a lower risk of Alzheimer's Disease."

Dr Reitz is a medical doctor and genetic epidemiologist. Her research focuses on the identification of genetic and non-genetic factors that contribute to Alzheimer's disease, frontotemporal lobar degeneration, and structural and functional brain changes.

Dr Reitz concluded: "Higher levels of total cholesterol were associated with a decreased risk of incident Alzheimer's Disease."

Alzheimer’s patients have significantly reduced levels of cholesterol and fats in the brain

This study was published in Alzheimer Disease and Associated Disorders 1998 Sep;12(3):198-203

Study title and authors:
Reduced levels of cholesterol, phospholipids, and fatty acids in cerebrospinal fluid of Alzheimer disease patients are not related to apolipoprotein E4.

Mulder M, Ravid R, Swaab DF, de Kloet ER, Haasdijk ED, Julk J, van der Boom JJ, Havekes LM.
Gaubius Laboratory, TNO-PG, Leiden, The Netherlands.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/9772023

The study compared levels of cholesterol and fats in cerebrospinal fluid (cerebrospinal fluid is found in the brain and spinal canal) in Alzheimers patients and subjects without Alzheimers. The study assessed the brain tissue at postmortem in 30 Alzheimers cases and 31 age-matched control patients.

The study found:
(a) Cholesterol levels in the cerebrospinal fluid of patients without alzheimer's was 55% higher than in patients with Alzheimer's.
(b) Fatty acid levels (fat molecules) in the cerebrospinal fluid of patients without alzheimer's was 522% higher than in patients with Alzheimer's.
(c) Phospholipid levels (phospholipids contain two molecules of fat and are a major component of cell membranes) in the cerebrospinal fluid of patients without alzheimer's was 1650% higher than in patients with Alzheimer's.

The results of the study show that Alzheimer’s patients have significantly reduced levels of cholesterol and fats in the cerebrospinal fluid.

Shortage of cholesterol linked to neurodegenerative diseases

This post includes a synopsis of a paper published in Neurobiology of Disease 2009 May;34(2):212-20

Study title and authors:
Aneuploidy in the normal, Alzheimer's disease and ataxia-telangiectasia brain: differential expression and pathological meaning.

Iourov IY, Vorsanova SG, Liehr T, Yurov YB.

National Research Center of Mental Health, Russian Academy of Medical Sciences, Moscow, Russia.ivan_iourov@yahoo.com

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/19344645

Aneuploid cells have an abnormal number of chromosomes and may form because of a shortage of cholesterol. See here.

The study measured the number of aneuploid cells in the brains of people with:
(a) No disease
(b) Alzheimer's disease
(c) Ataxia Telangiectasia

The study revealed that:
(1) The overall proportion of aneuploid cells in the normal brain is approximately 10%.
(2) The overall proportion of aneuploid cells in the brain of ataxia telangiectasia individuals was estimated at approximately 20-50%.
(3) A dramatic 10-fold increase of chromosome 21-specific aneuploidy was detected in individuals with Alzheimer's disease.

Iourov concluded that neural aneuploidy to be a feature of neurodegenerative diseases.

Cholesterol is essential for renewal of cells and wound healing

This study was published in Experimental Cell Research Volume 300, Issue 1, 15 October 2004, Pages 109-120

Study title and authors:
Cholesterol is essential for mitosis progression and its deficiency induces polyploid cell formation
Carlos Fernández, María del Val T. Lobo, c, Diego Gómez-Coronado and Miguel A. Lasunción, d,
Servicio de Bioquímica-Investigación, Hospital Ramón y Cajal, Madrid, Spain

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/15383319

Fernández notes that cholesterol is an essential component of cell membranes.

Mitosis is a process of cell division which results in the production of two daughter cells from a single parent cell. The daughter cells are identical to one another and to the original parent cell. Mitosis plays a role in cell replacement and wound healing. Cytokinesis is the final stage of mitosis where a single parent cell forms the two new cells.

The aim of the study was to determine the role of cholesterol in mitosis. For this human cells were incubated in a cholesterol free medium and the results observed were:

(a) Prolonged cholesterol starvation inhibitied cytokinesis and caused the formation of polyploid cells, which were multinucleated (cells which have more than one nucleus per cell and are implicated in tumour formation) and had other abnormalities.
(b) Supplementing with cholesterol completely abolished these adverse effects, demonstrating they were specifically due to cholesterol deficiency.

Polyploid cells are implicated in cancer, Alzheimer's disease and ataxia telangiectasia (Ataxia-telangiectasia is rare childhood disease that affects the brain and other parts of the body such as uncoordinated movements and retarded mental ability)

Fernández concluded: "Cholesterol is essential for mitosis completion and that, in the absence of cholesterol, the cells fail to undergo cytokinesis... generating polyploid cells".

Cholesterol deficiency may lead to the development of Alzheimer's

This post contains a summary of a paper published in the European Journal of Internal Medicine 22 (2011) 134-140

Study title and authors:
Nutrition and Alzheimer's disease: The detrimental role of a high carbohydrate diet
Stephanie Seneff , Glyn Wainwright , Luca Mascitelli ,
Department of Electrical Engineering and Computer Science, MIT Cambridge, MA, USA

This paper can be accessed at: http://www.lizscript.co.uk/glyn/EJIM01.pdf

In this paper, the authors highlight how an excess of dietary carbohydrates, particularly fructose, alongside a relative deficiency in dietary fats and cholesterol, may lead to the development of Alzheimer's disease.

The lead author of the study, Dr Stephanie Seneff, explains
(a) The first step in Alheimer's is represented by advanced glycation end-products in crucial plasma proteins concerned with fat, cholesterol, and oxygen transport.
(b) This leads to cholesterol deficiency in neurons, which significantly impairs their ability to function.
(c) Over time this may lead to increased oxidative damage, mitochondrial and lysosomal dysfunction, increased risk to microbial infection, and, ultimately, cell death.

Dr Seneff concluded: "Other neurodegenerative diseases share many properties with Alzheimer's disease, and may also be due in large part to this same underlying cause".

High cholesterol levels associated with a decreased risk of Alzheimers disease

This study was published in the Archives of Neurology 2010 Dec;67(12):1491-7

Study title and authors:
Association of higher levels of high-density lipoprotein cholesterol in elderly individuals and lower risk of late-onset Alzheimer disease.
Reitz C, Tang MX, Schupf N, Manly JJ, Mayeux R, Luchsinger JA.
Gertrude H. Sergievsky Center, Columbia University, New York, NY 10032, USA. cr2101@columbia.edu

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/21149810

The study examined the association of cholesterol levels with Alzheimer disease. The study included 1,130 men and women (who were free of cognitive impairment at the start of the study) aged 65 or over with 4,469 person-years of follow-up.

The study found:
(a) Those with the highest total cholesterol levels had a 20% decreased risk of developing Alzheimers compared to those with the lowest total cholesterol levels.
(b) Those with the highest high density lipoprotein (HDL) cholesterol levels had a 60% decreased risk of developing Alzheimers compared to those with the lowest high density lipoprotein (HDL) cholesterol levels.
(c) Those with the highest low density lipoprotein (LDL) cholesterol levels had a 10% decreased risk of developing Alzheimers compared to those with the lowest loe density lioprotein (LDL) cholesterol levels.

The results of the study show that high levels of total cholesterol, HDL cholesterol LDL cholesterol are associated with a decreased risk of Alzheimers disease.