ABSTRACT
Cholesterol and the immune system are involved in Alzheimer's Disease (AD). To investigate the relations among them, we compared the cholesterol content in peripheral blood mononuclear cells (PBMC) of cognitively healthy controls and patients with mild cognitive impairment (MCI) and AD in two independent samples. Free cholesterol content of PBMC was lower in MCI and AD patients, and was modulated by APOE genotype. A decrease of CD8+ and an increase of CD16+ was also found in AD patients. These results suggest that cholesterol levels in PBMCs may represent an early signature of the disease and support the involvement of immune system in AD.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/genetics , Leukocytes, Mononuclear , Cholesterol , BiomarkersABSTRACT
INTRODUCTION: The APOE epsilon4 allele is a well-established risk factor for Alzheimer's disease. This disease is characterized by a typical progressive cognitive impairment pattern, different from that of other primary dementias such as dementia with Lewy bodies or frontotemporal and vascular dementias, for which there are no conclusive results on the influence of the APOE genotype. OBJECTIVE: Our aim is to study how the APOE genotype associates with different dementia types, and the association of this genotype with mild cognitive impairment and age related cognitive decline, which might be stages in a continuum between normality and dementia. PATIENTS AND METHODS: From a group of 1,022 people we selected 733 patients with different dementia diagnosis and 205 controls. APOE genotype for each participant in the study was determined. RESULTS: As it was already known, the epsilon4 allele is associated to senile Alzheimer's disease (OR= 5.6; 95% CI= 3.6-8.9; p< 0.001) and presenile Alzheimer's disease (OR= 5.4; 95% CI= 2.1-13.8; p< 0.001). It is also associated to mild cognitive impairment (OR= 3.7; 95% CI= 2.3-6.0; p< 0.001) and to age related cognitive decline (OR= 3.0; 95% CI= 1.2-7.3; p< 0.01). Female Alzheimer patients with at least one epsilon4 allele present significantly an earlier age at onset (epsilon4+= 73.4 +/- 5.4; epsilon4- = 76.9 +/- 5.5; p< 0.001). CONCLUSION: The APOE genotype is associated to Alzheimer's disease and to its cognitive impairment pattern. This association has a growing value according to the degree of clinical impairment. The APOE genotype could be used in differential diagnostic of cognitive impairment.
Subject(s)
Apolipoproteins E/metabolism , Cognition Disorders/genetics , Cognition Disorders/physiopathology , Dementia/genetics , Dementia/physiopathology , Age of Onset , Aged , Aging/physiology , Alzheimer Disease/genetics , Alzheimer Disease/physiopathology , Apolipoprotein E4 , Apolipoproteins E/genetics , Cognition Disorders/diagnosis , Dementia/classification , Dementia/diagnosis , Female , Genotype , Humans , Male , Middle Aged , Risk FactorsABSTRACT
Introducción. El alelo e4 de la APOE es un factor de riesgo bien establecido para la enfermedad de Alzheimer (EA). Esta enfermedad se caracteriza por un patrón de deterioro cognitivo (DC)progresivo bastante típico, diferente del de otras demencias, como la demencia con cuerpos de Lewy, la demencia frontotemporal o la demencia vascular, en las que no se han obtenido resultados concluyentes sobre la influencia de este gen. Objetivo. Estudiar la asociación del genotipo APOE con diferentes tipos de demencia, y la asociación de este genotipo con el deterioro cognitivo ligero (DCL) y eldeterioro cognitivo asociado a la edad (DECAE), posibles estadios de un continuo entre la normalidad y la demencia. Pacientes y métodos. Se reclutaron 1.022 personas, de las que se seleccionaron 733 pacientes con distintos subtipos de demencia y 205 controles, a los que se determinó el genotipo del APOE. Resultados. Como ya se conocía, el alelo e4 se asocia a la EA de edad de inicio senil (OR = 5,6; IC 95 por ciento = 3,6-8,9; p < 0,001) y presenil (OR = 5,4; IC 95 por ciento = 2,1-13,8; p < 0,001). También se asocia al DCL (OR = 3,7; IC 95 por ciento = 2,3-6,0; p < 0,001) y al DECAE (OR = 3,0; IC 95 por ciento = 1,2-7,3; p < 0,01). La edadde inicio de la EA es significativamente inferior en las pacientes que poseen al menos un alelo e4 (e4+ = 73,4 ñ 5,4; e4- = 76,9 ñ 5,5; p <0,001). Conclusiones. El genotipo APOE se asocia a la EA y alpatrón de deterioro que la caracteriza. Esta asociación tiene un valor creciente según el grado de deterioro objetivable. El genotipo APOE podría servir en el diagnóstico diferencial del DC (AU)
Introduction. The APOE e4 allele is a well-established risk factor for Alzheimers disease. This disease is characterized by a typical progressive cognitive impairment pattern, different from that of other primary dementias such as dementia with Lewy bodies or frontotemporal and vascular dementias, for which there are no conclusive results on the influence of the APOE genotype. Objective. Our aim is to study how the APOE genotype associates with different dementia types, and the asso ciation of this genotype with mild cognitive impairment and age-related cognitive decline, which might be stages in a continuum between normality and dementia. Patients and methods. From a group of 1.022 people we selected 733 patients with different dementia diagnosys and 205 controls. APOE genotype for each participant in the study was determined. Results. As it was already known, the e4 allele is associated to senile Alzheimers disease (OR = 5,6; 95% CI = 3,6-8,9; p < 0,001) and presenile Alzheimers disease (OR = 5,4; 95% CI = 2,1-13,8; p < 0,001). It is also associated to mild cognitive impairment (OR = 3,7; 95% CI = 2,3-6,0; p < 0,001) and to age-related cognitive decline (OR = 3,0; 95% CI = 1,2-7,3; p < 0,01). Female Alzheimer patients with at least one e4 allele present significantly an earlier age at onset (e4 + = 73,4 ± 5,4; e4 - = 76,9 ± 5,5; p < 0,001). Conclusion. The APOE genotype is associated to Alzheimers disease and to its cognitive impairment pattern. This association has a growing value according to the degree of clinical impairment. The APOE genotype could be used in differential diagnostic of cognitive impairment (AU)
Subject(s)
Female , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Neuropsychological Tests , Neuropsychological Tests , Alzheimer Disease , Risk Factors , Surveys and Questionnaires , Mass Screening , Apolipoproteins E , Genotype , Cognition Disorders , Geriatric Assessment , Regression Analysis , ROC Curve , Age of Onset , Social Class , Dementia , Reproducibility of Results , Sensitivity and Specificity , Aging , Geriatric Assessment , Predictive Value of TestsABSTRACT
Introducción. Algunas formas de miastenia gravis y un gran número de los casos de síndrome de Eaton-Lambert contituyen trastornos de la transmisión neuromuscular con posible origen paraneoplásico. Las miopatías paraneoplásicas son la miopatía necrotizante paraneoplásica y algunos casos de miopatía inflamatoria (polimiositis-dermatomiositis). Desarrollo. Todos estos procesos poseen una naturaleza autoinmune. El diagnóstico es clínico, y se basa fundamentalmente en las características de la debilidad o del trastorno motor, confirmado por métodos serológicos (demostración de autoanticuerpos), pruebas farmacológicas, electromiografía, estudios de imagen y, en algunos casos, biopsia. El tratamiento comprende medidas sintomáticas específicas (dirigidas a corregir el defecto en la transmisión neuromuscular en los síndromes miasténicos, a disminuir la autoexcitabilidad axonal en los de hiperexcitabilidad neuromuscular, etc.) y patogénicas (fundamentalmente inmunosupresión). La búsqueda de un tumor oculto debe ser una parte más del trabajo diagnóstico. La enfermedad paraneoplásica puede remitir con el tratamiento de dicho tumor (AU)
Subject(s)
Humans , Thymoma , Stiff-Person Syndrome , Lambert-Eaton Myasthenic Syndrome , Muscle, Skeletal , Motor Endplate , Myasthenia Gravis , Polyradiculoneuropathy , Neuromuscular Diseases , Autoimmune Diseases of the Nervous System , Isaacs Syndrome , Dermatomyositis , Thymus Neoplasms , Neoplasms, Unknown PrimaryABSTRACT
INTRODUCTION: Some forms of myasthenia gravis and many cases of Eaton-Lambert syndrome are disorders of neuromuscular transmission possibly of paraneoplastic origin. Paraneoplastic necrotizing myopathy and some cases of inflammatory myopathy (polymyositis-dermatomyositis) are paraneoplastic myopathies. DEVELOPMENT: These are all autoimmune processes. The diagnosis is clinical, based mainly on the characteristics of the muscle weakness and motor disorders, confirmed by serological methods (demonstration of antibodies) pharmacological and electromyographic tests, by imaging studies and in some cases biopsy. Treatment includes specific symptomatic measures (aimed at correcting the defect in neuromuscular transmission in the myasthenic syndromes, reducing axonal auto-excitability in the neuromuscular hyperexcitability syndromes, etc.) and pathogenic treatment (basically immunosuppression). A search for the hidden tumour should also be part of the diagnostic investigation. The paraneoplastic disease may remit if the associated tumour is treated.