Enhancing Alzheimer's Disease Diagnosis and Care by Focusing on Plasma Biomarkers for Identifying Mild Cognitive Impairment.

Biomarkers that accurately identify mild cognitive impairment (MCI) are of greater importance for Alzheimer's disease (AD) management and treatment. On the other hand, blood-based biomarkers are not only more practical but also less invasive than the common cerebrospinal fluid biomarkers. In their report in the Journal of Alzheimer's Disease, Wang and collaborators identified 67 upregulated and 220 downregulated long noncoding RNAs (lncRNAs).

APOEɛ4-TOMM40L Haplotype Increases the Risk of Mild Cognitive Impairment Conversion to Alzheimer's Disease.

Background: Mild cognitive impairment (MCI) has been considered as a pre-dementia stage, although the factors leading to Alzheimer's disease (AD) conversion remain controversial.

Objective: Evaluate whether TOMM40 poly-T (TOMM40' 523) polymorphism is associated with the risk and conversion time from MCI to AD and secondly with AD cerebrospinal fluid (CSF) biomarkers, disentangling the APOE genotype.

Methods: 147 AD patients, 102 MCI patients, and 105 cognitively normal controls were genotyped for poly-T polymorphism.

Underlying Biological Processes in Mild Cognitive Impairment: Amyloidosis Versus Neurodegeneration.

The amyloid cascade hypothesis proposes amyloid-β (Aβ) as the earliest and key pathological hallmark of Alzheimer's disease (AD), but this mandatory "amyloid-first pathway" has been contested. Longitudinal studies of mild cognitive impairment (MCI) patients represent an opportunity to investigate the intensity of underlying biological processes (amyloidosis versus neurodegeneration) and their relevance for progression to AD. We re-examined our cohort of amnestic MCI, grouped according to cerebrospinal fluid (CSF) biomarkers, aiming at establishing their prognostic value for Alzheimer-type dementia and testing the hypothetical model of biomarkers sequence, based on the amyloid cascade.

Addition of the Aβ42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer's disease dementia in mild cognitive impairment.

Background: Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer's disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aβ42 concentration to the level of total amyloid beta (Aβ), using the Aβ42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia.

Brain GLP-1/IGF-1 Signaling and Autophagy Mediate Exendin-4 Protection Against Apoptosis in Type 2 Diabetic Rats.

Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues. One of them is the brain, whose dysfunctional intracellular quality control mechanisms (namely autophagy) may upregulate apoptosis, leading to cognitive dysfunction and Alzheimer disease (AD). Since impaired brain insulin signaling may constitute the crosslink between T2D and AD, its restoration may be potentially therapeutic herein.

[Relevant Factors on Cognitive Evaluation of the Portuguese Population].

Introduction: Aging is an inevitable process that has a social impact in the forecoming decades, and it will present a great challenge regarding public health. An efficient health system requires a reflection on the preventive measures to be implemented.

Material And Methods: The study population comprised a total number of 2672 individuals of both genders, aged 55 years and over, residents in continental Portugal, to whom a questionnaire was applied that included the following sections: Social network; Locomotion; Physical autonomy; Instrumental autonomy; Cognitive assessment; Physical activity.

Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment.

This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3) interpretation of results, and 4) patient counseling. The working group recommended using CSF AD biomarkers in the diagnostic workup of MCI patients, after prebiomarker counseling, as an add-on to clinical evaluation to predict functional decline or conversion to AD dementia and to guide disease management.

Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia.

This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β, tau, and phosphorylated tau in the diagnostic evaluation of patients with dementia. The recommendations were developed by a multidisciplinary working group based on the available evidence and consensus from focused discussions for (i) identification of Alzheimer's disease (AD) as the cause of dementia, (ii) prediction of rate of decline, (iii) cost-effectiveness, and (iv) interpretation of results. The working group found sufficient evidence to support a recommendation to use CSF AD biomarkers as a supplement to clinical evaluation, particularly in uncertain and atypical cases, to identify or exclude AD as the cause of dementia.

Improved Cerebrospinal Fluid-Based Discrimination between Alzheimer's Disease Patients and Controls after Correction for Ventricular Volumes.

Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e.

Cerebrospinal fluid Aβ40 is similarly reduced in patients with Frontotemporal Lobar Degeneration and Alzheimer's Disease.

Cerebrospinal fluid (CSF) biomarkers have been increasingly studied for dementia diagnosis, however the accuracy to distinguish between different forms of dementia is still unsatisfactory. In this study, the added value of another CSF Aβ-peptide (Aβ40), along with the core CSF markers t-Tau, p-Tau, and Aβ42, in the discrimination between two large dementia groups of Frontotemporal Lobar Degeneration (FTLD; n=107), Alzheimer's Disease (AD; n=107) and non-demented subjects (n=33) was evaluated. In FTLD, t-Tau and p-Tau were significantly increased in relation to controls, but lower than in AD, while Aβ42 was similar in FTLD and controls, but higher than in AD.

Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers.

Introduction: Core cerebrospinal fluid (CSF) biomarkers - Aβ42, Tau, and phosphorylated Tau (pTau) - have been recently incorporated in the revised criteria for Alzheimer's disease (AD). However, their widespread clinical application lacks standardization. Pre-analytical sample handling and storage play an important role in the reliable measurement of these biomarkers across laboratories.

Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide.

Long-acting glucagon-like peptide-1 (GLP-1) analogues marketed for type 2 diabetes (T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia.

Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study.

Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program - Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis.

Vascular, oxidative, and synaptosomal abnormalities during aging and the progression of type 2 diabetes.

Alterations in brain structure and function are a well-known long-term complication of type 2 diabetes (T2D). Although the mechanism(s) by which T2D lead(s) to cognitive dysfunction and neuronal cells degeneration continue(s) to be a matter of debate, vascular alterations emerged as major players in this scenario. This study was aimed to evaluate the antioxidant defenses and oxidative markers present in brain vessels and synaptosomes from 3- and 12-month-old Goto- Kakizaki (GK) rats, a spontaneous non-obese model of T2D, and Wistar control rats.

The aging profile of the Portuguese population: a principal component analysis.

In the last 5 years the resident population of Portugal has increased 2.3%, along with a progressive ageing. This study aims assessing the social dependence and frailty, as well as social and familial support needs of the elderly.

Progranulin peripheral levels as a screening tool for the identification of subjects with progranulin mutations in a Portuguese cohort.

Background: Progranulin (PGRN) mutations are associated with different clinical phenotypes, including frontotemporal lobar degeneration (FTLD), corticobasal syndrome (CBS) and Alzheimer's disease (AD). As all pathogenic PGRN mutations identified so far cause disease through haploinsufficiency, determination of PGRN levels has been proposed as a reliable method to identify mutation carriers.

Objective: To evaluate the accuracy of peripheral PGRN levels in the identification of the PGRN mutation carriers detected thus far in our Portuguese cohort.

Amplified and homozygously deleted genes in glioblastoma: impact on gene expression levels.

Background: Glioblastoma multiforme (GBM) displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown.

Methodology: Single-nucleotide polymorphism (SNP)-arrays were used to determine the frequency of recurrent amplicons and homozygous deletions in GBM (n = 46), and to evaluate the impact of copy number alterations (CNA) on mRNA levels of the genes involved.

Principal Findings: Recurrent amplicons were detected for chromosomes 7 (50%), 12 (22%), 1 (11%), 4 (9%), 11 (4%), and 17 (4%), whereas homozygous deletions involved chromosomes 9p21 (52%) and 10q (22%).

Detailed characterization of alterations of chromosomes 7, 9, and 10 in glioblastomas as assessed by single-nucleotide polymorphism arrays.

Glioblastomas are cytogenetically heterogeneous tumors that frequently display alterations of chromosomes 7, 9p, and 10q. We used high-density (500K) single-nucleotide polymorphism arrays to investigate genome-wide copy number alterations and loss of heterozygosity in 35 primary glioblastomas. We focused on the identification and detailed characterization of alterations involving the most frequently altered chromosomes (chromosomes 7, 9, and 10), the identification of distinct prognostic subgroups of glioblastomas based on the cytogenetic patterns of alteration for these chromosomes, and validation of their prognostic impact in a larger series of tumors from public databases.

Cross-talk between mitochondria and proteasome in Parkinson's disease pathogenesis.

Parkinson's disease (PD) is the most common progressive neurodegenerative movement disorder, characterized by the selective loss of nigrostriatal dopaminergic neurons, and the presence of intracellular insoluble proteinaceous inclusions, known as Lewy Bodies. Although PD etiopathogenesis remains elusive, the leading hypothesis for the death of specific groups of neurons establishes that mitochondrial dysfunction, alterations in the ubiquitin-proteasomal system (UPS), and oxidative stress are major events that act synergistically causing this devastating disease. In this review we will focus on mitochondrial impairment and its implications on proteasomal function and alpha-synuclein aggregation.

A socio-demographic study of aging in the Portuguese population: the EPEPP study.

The increase in life expectancy (LE) observed in Western societies, has resulted in a steep rise of older population. This stresses the importance of the research on aging, to better adequate health and social care organization and improve the quality of life (QoL). The aim of the EPEPP-1 (abbreviated from the Portuguese name: Estudo do Perfil de Envelhecimento da População Portuguesa) study was to characterize the socio-demographic components of the elderly Portuguese population in order to disclose factors that could play a role in the aging process and in the elderly QoL.

Value of brain magnetic resonance imaging in mitochondrial respiratory chain disorders.

Mitochondrial respiratory chain (MRC) disorders have variable clinical manifestations which are mainly neurologic. Diagnosis in children is more complex than in adults because the classic phenotype, ragged red fibers, and mtDNA mutations are rarely seen in children. Moreover, clinical manifestations of disease in developing brains are less explicit.