Imaging biomarkers in neurodegeneration: current and future practices.

There is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo investigation of neurodegenerative disorders has increased substantially over the past decades and continues to provide further benefits both to the diagnosis and understanding of these diseases. This review forms part of a series of articles which stem from the University College London/University of Gothenburg course "Biomarkers in neurodegenerative diseases".

Tau Positron Emission Tomography Binding Is Not Elevated in HIV-Infected Individuals.

Regional standardized uptake value ratios (SUVRs) for tau positron emission tomography (PET) were compared among 19 cognitively normal human immunodeficiency virus (HIV)-negative control individuals, 20 HIV-negative patients with symptomatic Alzheimer disease, 15 cognitively normal HIV-positive individuals, and 17 cognitively impaired HIV-positive individuals. Among the HIV-positive participants, the correlation between tau PET SUVRs and both HIV loads and CD4+ T-cell counts (recent and nadir). Tau PET SUVRs were similar for HIV-positive individuals and HIV-negative control individuals.

Loss of white matter integrity reflects tau accumulation in Alzheimer disease defined regions.

Objective: White matter (WM) projections were assessed from Alzheimer disease (AD) gray matter regions associated with β-amyloid (Aβ), tau, or neurodegeneration to ascertain relationship between WM structural integrity with Aβ and/or tau deposition.

Methods: Participants underwent diffusion tensor imaging (DTI), PET Aβ ([F]AV-45 [florbetapir]), and PET tau ([F]AV-1451 [flortaucipir]) imaging. Probabilistic WM summary and individual tracts were created from either a composite or individual gray matter seed regions derived from Aβ, tau, and neurodegeneration.

In vivo [F]-AV-1451 tau-PET imaging in sporadic Creutzfeldt-Jakob disease.

Objective: To determine whether specific patterns of [F]-AV-1451 tau-PET retention are observed in patients with autopsy-proven sporadic Creutzfeldt-Jakob disease (CJD).

Methods: In vivo [F]-AV-1451 PET neuroimaging was performed in 5 patients with sporadic CJD (median age, 66 years [63-74]), and results were compared to cognitively normal (CN) persons (n = 44; median age, 68 years [63-74]) and to participants with very mild Alzheimer disease (AD) dementia (n = 8; median age, 77 years [63-90]). Autopsy was completed in all patients with CJD, confirming the clinical diagnosis and permitting characterization of AD neuropathologic change (ADNC).

Frontotemporal lobar degeneration and social behaviour: Dissociation between the knowledge of its consequences and its conceptual meaning.

Inappropriate social behaviour is an early symptom of frontotemporal lobar degeneration (FTLD) in both behavioural variant frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Knowledge of social behaviour is essential for appropriate social conduct. The superior anterior temporal lobe (ATL) has been identified as one key neural component for the conceptual knowledge of social behaviour, but it is unknown whether this is dissociable from knowledge of the consequences of social behaviour.

Arterial spin labelling shows functional depression of non-lesion tissue in chronic Wernicke's aphasia.

Behavioural impairment post-stroke is a consequence of structural damage and altered functional network dynamics. Hypoperfusion of intact neural tissue is frequently observed in acute stroke, indicating reduced functional capacity of regions outside the lesion. However, cerebral blood flow (CBF) is rarely investigated in chronic stroke.

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2).

Concordant association of insulin degrading enzyme gene (IDE) variants with IDE mRNA, Abeta, and Alzheimer's disease.

Background: The insulin-degrading enzyme gene (IDE) is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD).

Methodology/principal Findings: We examined conserved regions of IDE and its 10 kb flanks in 269 AD cases and 252 controls thereby identifying 17 putative functional polymorphisms. These variants formed eleven haplotypes that were tagged with ten variants.

Homocysteine as a predictor of cognitive decline in Alzheimer's disease.

Objective: Moderately elevated levels of plasma total homocysteine are associated with an increased risk of developing Alzheimer's disease. We have tested whether baseline concentrations of homocysteine relate to the subsequent rate of cognitive decline in patients with established Alzheimer's disease (AD).

Methods: In 97 patients with AD, 73 pathologically-confirmed, we analysed the decline of global cognitive test scores (CAMCOG) over time from the first assessment for at least three 6-monthly visits up to a maximum of 9.

PSEN1 polymorphisms alter the rate of cognitive decline in sporadic Alzheimer's disease patients.

Mutations in amyloid precursor protein (APP) and presenilin (PSEN) genes are known to cause familial early-onset Alzheimer's disease (AD), which account for around 5% of AD cases. Genetic associations for the remaining "sporadic" cases, other than the risks associated with the apolipoprotein (APOE) epsilon4 allele are currently not fully established. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in PSEN1 are associated with a modified risk for sporadic AD or a modified disease phenotype.

Regulatory region single nucleotide polymorphisms of the apolipoprotein E gene and the rate of cognitive decline in Alzheimer's disease.

The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the regulatory regions of the apolipoprotein E (APOE) gene modify the well-established epsilon4-associated risk for Alzheimer's disease (AD). Sequencing of the APOE gene regulatory regions revealed four previously reported promoter SNPs and one novel SNP in the previously described macrophage enhancer (ME.1).

Susceptibility groups for Alzheimer's disease (OPTIMA cohort): integration of gene variants and biochemical factors.

Information on gene variants and blood levels (APOE, BCHE-K, TF-C2, HFE-D, HFE-Y, ACE I/D, AR1; homocysteine, folate and vitamin B(12)) is available for participants in the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort (n=575). This information identified four risk sets for Alzheimer's disease (AD) using grade of membership analysis (GoM). Graded membership scores that relate individuals to each set are automatically generated.