%0 Journal Article %J J Alzheimers Dis %D 2018 %T ABC Transporters Are Key Players in Alzheimer's Disease. %A Pereira, Cátia D %A Martins, Filipa %A Wiltfang, Jens %A da Cruz E Silva, Odete A B %A Rebelo, Sandra %K Alzheimer Disease %K Amyloid beta-Peptides %K Animals %K ATP-Binding Cassette Transporters %K Blood-Brain Barrier %K Humans %X

Human ATP-binding cassette (ABC) transporters mediate a critical function in the cell, namely the transport of molecules across lipid membranes. Associated to their ubiquitous tissue distribution, they are key players in cellular homeostasis but also potential causative or contributing factors for many pathologies, including Alzheimer's disease (AD). In the central nervous system (CNS), numerous ABC transporters are present throughout the brain parenchyma and especially at the blood-brain barrier (BBB). AD is a neurodegenerative disorder mainly characterized by extracellular deposition of amyloid-β (Aβ) peptides and intracellular accumulation of hyperphosphorylated forms of tau protein. Besides being degraded via proteolytic and phagocytic processes mediated by brain parenchymal cells, a major mechanism for eliminating cerebral Aβ is through its transport across the BBB into the peripheral blood. In fact, many AD cases are associated with impaired Aβ clearance. Consistently, several studies have recently uncovered important roles for ABC transporters in AD pathophysiology. Hence, this review focuses on the relevance of ABC transporters in CNS homeostasis by highlighting AD as a strong example of the deleterious consequences that might result from the former's altered expression and/or activity in the brain. The potentiality of human ABC transporters as novel pharmacological targets for both the diagnosis and therapeutics of AD is emphasized.

%B J Alzheimers Dis %V 61 %P 463-485 %8 2018 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/29171999?dopt=Abstract %R 10.3233/JAD-170639 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Putative Dementia Cases Fluctuate as a Function of Mini-Mental State Examination Cut-Off Points. %A Rosa, Ilka M %A Henriques, Ana G %A Wiltfang, Jens %A da Cruz E Silva, Odete A B %K Age Factors %K Aged %K Aged, 80 and over %K Cohort Studies %K Community Health Planning %K Cross-Sectional Studies %K Dementia %K Female %K Humans %K Male %K Mental Status and Dementia Tests %K Middle Aged %K Neuropsychological Tests %K ROC Curve %X

As the population ages, there is a growing need to quickly and accurately identify putative dementia cases. Many cognitive tests are available; among those commonly used are the Cognitive Dementia Rating (CDR) and the Mini-Mental Status Examination (MMSE). The aim of this work was to compare the validity and reliability of these cognitive tests in a primary care based cohort (pcb-Cohort). The MMSE and the CDR were applied to 568 volunteers in the pcb-Cohort. Distinct cut-off points for the MMSE were considered, namely MMSE 27, MMSE 24, and MMSE PT (adapted for the Portuguese population). The MMSE 27 identified the greatest number of putative dementia cases, and, as determined by the ROC curve, it was the most sensitive and specific of the MMSE cut-offs considered. Putative predictive or risk factors identified included age, literacy, depression, and diabetes mellitus (DM). DM has previously been indicated as a risk factor for dementia and Alzheimer's disease. Comparatively, the MMSE 27 cut-off has the greatest sensibility (94.9%) and specificity (66.3%) when compared to MMSE PT and MMSE 24. Upon comparing MMSE and CDR scores, the latter identified a further 146 putative dementia cases, thus permitting one to propose that in an ideal situation, both tests should be employed. This increases the likelihood of identifying putative dementia cases for subsequent follow up work, thus these cognitive tests represent important tools in patient care. Further, this is a significant study for Portuguese populations, where few of these studies have been carried out.

%B J Alzheimers Dis %V 61 %P 157-167 %8 2018 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/29125486?dopt=Abstract %R 10.3233/JAD-170501