Sporadic Creutzfeldt-Jakob disease with glial PrPRes nuclear and perinuclear immunoreactivity.

Proteinase K-resistant prion protein (PrPRes ) nuclear and perinuclear immunoreactivity in oligodendrocytes of the frontal cortex is found in one case of otherwise typical sporadic Creutzfeldt-Jakob disease (sCJD) type VV2a. The PrP nature of the inclusions is validated with several anti-PrP antibodies directed to amino acids 130-160 (12F10), 109-112 (3F4), 97-102 (8G8) and the octarepeat region (amino acids 59-89: SAF32). Cellular identification and subcellular localization were evaluated with double- and triple-labeling immunofluorescence and confocal microscopy using antibodies against PrP, glial markers, and histone H3. Based on review of the literature and our own experience, this is a very odd situation that deserves further validation in other cases.

Sobre el famoso «triángulo» de Mollaret / Regarding the famous triangle of Guillain-Mollaret

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[Where does Parkinson's disease start?]. / Dónde comienza la enfermedad de Parkinson?

Parkinson's disease concept is classically restricted to a rigid-akinetic syndrome due to a nigro-striatal dopaminergic depletion. This concept ignored the widespread extension of neuropathologic findings across the CNS. Moreover detailed clinical studies showed that patients suffer a constellation of other symptoms and signs such as anosmia, constipation, cardiovascular disautonomia, neuropsychologic and neuropsychiatric disorders, dementia and sleep changes. Taken together these evidences have lead to the idea that Parkinson's disease is a multisystemic disease of the nervous system. Braak et al. have proposed first, a staging system for the neuropathologic burden into the CNS and second, a "dual-hit" pathogenic hypothesis implicating a putative exogenous agent acquired through nasal route passing into the digestive tube and reaching the medulla following the vagus nerve. This hypothesis has received many criticisms. Our own findings in a family carrying a single aminoacid change (E46K) in alpha-synuclein segregating with a severe autosomal dominant Parkinson's disease phenotype, suggest that cardiac sympathetic denervation is the first step in this disease.

Risk factors for dementia in the epidemiological study of Munguialde County (Basque Country-Spain).

BACKGROUND: Prevalence of degenerative dementias and dementias associated with cerebrovascular disease is increasing. Dementia is one of the most significant public health problem. In recent years, the role of vascular risk factors (hypertension, diabetes mellitus and hypercholesterolemia) and depression has been evaluated.The incidence of dementia and risk factors has not been fully investigated in Spain. The aim of this study was to identify the risk factors for dementia, Alzheimer's disease (AD) and vascular dementia (VD) in elderly people in Munguialde County (Spain). METHODS: A two phase, door-to-door populational study was performed. Demographic variables and the presence of vascular risk factors and depression were recorded. The MMSE, the DSM-IV and the conventional criteria for AD and VD were used in the evaluation. The odds ratio for each risk factor was calculated by logistic regression analysis. RESULTS: 1756 healthy subjects and 175 patients with dementia participated in the study. Of these, 133 had AD, 15 VD and the remainder other dementias. The risk factors for dementia and AD were female sex (OR = 1.67 and 1.97, respectively); age (OR = 1.14 and 1.15); stroke (OR = 7.84 and 3); and depression (OR = 53.08 and 3.19). Stroke was the only risk factor for VD (OR = 119). CONCLUSION: Greater age, female sex, stroke and depression increase the risk of suffering dementia, AD and VD. The relationship between depression, vascular risk factors and dementia has clear public health implications. Prevention and early treatment of vascular risk factors and depression may have an important impact in lowering the risk of dementia and could modify the natural history of the disease.

Prevalence of neuropsychiatric symptoms in elderly patients with dementia in Mungialde County (Basque Country, Spain).

BACKGROUND: Determination of the prevalence of neuropsychiatric symptoms in elderly patients with dementia in Mungialde. METHODS: 108 subjects with dementia, who participated in a door-to-door epidemiological study, were included. The 12-item Spanish version of the Neuropsychiatric Inventory was used to evaluate these symptoms. RESULTS: The prevalence of at least 1 neuropsychiatric symptom was found to be 76.90% for all dementia types, 73.50% in patients with Alzheimer's disease (AD), 80% for the Parkinson-Lewy body dementia complex (PLBD), 78.60% for vascular dementia (VD) and 100% for frontotemporal dementia (FTD). Apathy was found to be the most prevalent symptom for all dementia types and in patients with AD (53.70 and 54.30%, respectively). The next most prevalent symptoms were anxiety, depression and sleep disturbances (35.20, 32.40 and 30.60%) for all dementia types, and anxiety and depression (32.10 and 30.90%) in patients with AD. The most prevalent symptoms in patients with PLBD were apathy, appetite changes, sleep disturbances and agitation (50% each); in patients with VD they were apathy, depression and anxiety (42.90% each), and in patients with FTD they were apathy, anxiety and aberrant motor activity (100% each). CONCLUSIONS: Neuropsychiatric symptoms were found to be prevalent in patients with dementia, irrespective of dementia type.

Polymorphism in the cholesterol 24S-hydroxylase gene (CYP46A1) associated with the APOEpsilon3 allele increases the risk of Alzheimer's disease and of mild cognitive impairment progressing to Alzheimer's disease.

BACKGROUND: Late-onset Alzheimer's disease (LOAD) is associated with changes in certain proteins, such as ApoE and Cyp46A1, of the elimination route for cerebral cholesterol. The main lipoprotein involved in its transport is ApoE whose Epsilon4 allele is the least efficient. However, the presence or absence of this allele does not determine the development of LOAD, which implies the existence of other susceptibility factors associated with the disease, such as the CYP46A1 gene that encodes the enzyme cholesterol 24S-hydroxylase. OBJECTIVE: To find new data to contribute to the evaluation of whether the presence of the T allele in the polymorphic site rs754203 of the CYP46A1 gene leads to a greater risk of developing mild cognitive impairment (MCI) and LOAD. Furthermore, given the link between APOE and CYP46A1, we proceeded to relate both genotypes in each of the patient groups studied. METHODS: We studied MCI and LOAD patients and also carried out an analysis of those MCI patients who progressed from a mild cognitive deterioration to a clinically evident Alzheimer's disease during the study. RESULTS: The frequency of the CYP46A1-T allele in the LOAD patients with APOEpsilon3 alleles is significantly higher with respect to the control group; the same occurs in the group made up of LOAD patients together with the MCI patients who progressed to LOAD. The risk of developing LOAD when this allelic combination exists is 2.262 times higher (95% CI 1.337-4.202). However, having the CYP46A1-T allele does not increase the risk of suffering from LOAD in carriers of the APOEpsilon4 allele, probably because the transport of cholesterol is already affected in such patients and possibly masks the effect of the CYP46A1-T allele. CONCLUSIONS: The CYP46A1-T allele increases the risk of suffering from LOAD in persons carrying the APOEpsilon3 allele.