Regional distribution of synaptic markers and APP correlate with distinct clinicopathological features in sporadic and familial Alzheimer's disease.

Recent studies suggest that subcortical structures, including striatum, are vulnerable to amyloid-β accumulation and other neuropathological features in familial Alzheimer's disease due to autosomal dominant mutations. We explored differences between familial and sporadic Alzheimer's disease that might shed light on their respective pathogenic mechanisms. To this end, we analysed 12 brain regions, including neocortical, limbic and subcortical areas, from post-mortem brains of familial Alzheimer's disease (n = 10; age at death: 50.

Experience Corps Baltimore: Exploring the Stressors and Rewards of High-intensity Civic Engagement.

Purpose: Experience Corps (EC) represents a high-intensity, intergenerational civic engagement activity where older adults serve as mentors and tutors in elementary schools. Although high-intensity volunteer opportunities are designed to enhance the health and well being of older adult volunteers, little is known about the negative and positive aspects of volunteering unique to intergenerational programs from the volunteer's perspective.

Design And Methods: Stressors and rewards associated with volunteering in EC were explored in 8 focus group discussions with 46 volunteers from EC Baltimore.

Substrate steered crystallization of naphthyl end-capped oligothiophenes into nanofibers: the influence of methoxy-functionalization.

Naphthyl end-capped oligothiophenes are a class of materials well suited for high-performance organics based devices. The formation of nanofibers on muscovite mica from 2,5-bis(naphth-2-yl)thiophene (NaT), 5,5'-bis(naphth-2-yl)-2,2'-bithiophene (NaT2), and 5,5''-bis(naphth-2-yl)-2,2':5',2''-terthiophene (NaT3) as well as of the methoxy-functionalized variants MONaT, MONaT2, and MONaT3 is investigated via atomic force microscopy, X-ray diffraction, polarized fluorescence microscopy, and fluorescence spectroscopy. From polarized fluorescence microscopy spatially resolved molecular orientations are deduced revealing a profound anisotropy.

Degeneration of brainstem respiratory neurons in dementia with Lewy bodies.

Background: Respiratory dysfunction, including sleep disordered breathing, is characteristic of multiple system atrophy (MSA) and may reflect degeneration of brainstem respiratory nuclei involved in respiratory rhythmogenesis and chemosensitivity, including the pre-Bötzinger complex (preBötC), nucleus raphe pallidus (RPa), and nucleus raphe obscurus (ROb). However, impaired ventilatory responses to hypercapnia have also been reported in dementia with Lewy bodies (DLB), suggesting that these nuclei may also be affected in DLB.

Objectives: To determine whether there is involvement of the preBötC, RPa, and ROb in DLB.

TMEM106B protects C9ORF72 expansion carriers against frontotemporal dementia.

Variants in transmembrane protein 106 B (TMEM106B) modify the disease penetrance of frontotemporal dementia (FTD) in carriers of progranulin (GRN) mutations. We investigated whether TMEM106B is also a genetic modifier of disease in carriers of chromosome 9 open reading frame 72 (C9ORF72) expansions. We assessed the genotype of 325 C9ORF72 expansion carriers (cohort 1), 586 FTD patients lacking C9ORF72 expansions [with or without motor neuron disease (MND); cohort 2], and a total of 1,302 controls for TMEM106B variants (rs3173615 and rs1990622) using MassArray iPLEX and Taqman genotyping assays.

Directed self-assembled crystalline oligomer domains on graphene and graphite.

We observe the formation of thin films of fibre-like aggregates from the prototypical organic semiconductor molecule para-hexaphenylene (p-6P) on graphite thin flakes and on monolayer graphene. Using atomic force microscopy, scanning electron microscopy, x-ray diffraction, polarized fluorescence microscopy, and bireflectance microscopy, the molecular orientations on the surface are deduced and correlated to both the morphology as well as to the high-symmetry directions of the graphitic surface: the molecules align with their long axis at ±11° with respect to a high-symmetry direction. The results show that the graphene surface can be used as a growth substrate to direct the self-assembly of organic molecular thin films and nanofibres, both with and without lithographical processing.

Modelling longitudinal changes in older adults' memory for spoken discourse: findings from the ACTIVE cohort.

Episodic memory shows substantial declines with advancing age, but research on longitudinal trajectories of spoken discourse memory (SDM) in older adulthood is limited. Using parallel process latent growth curve models, we examined 10 years of longitudinal data from the no-contact control group (N = 698) of the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) randomised controlled trial in order to test (1) the degree to which SDM declines with advancing age, (2) the predictors of these age-related declines and (3) the within-person relationship between longitudinal changes in SDM and longitudinal changes in fluid reasoning and verbal ability over 10 years, independent of age. Individuals who were younger, were White, had more years of formal education, were male and had better global cognitive function and episodic memory performance at baseline demonstrated greater levels of SDM on average.

Structure-property relationship of anilino-squaraines in organic solar cells.

Soluble molecular semiconductors are a promising alternative to semiconducting polymers in the field of organic photovoltaics. Here, three custom-made symmetric 1,3-bis(N,N-alkylated-2,6-dihydroxy-anilino)squaraines containing systematic variations in their molecular structures are compared regarding their applicability as donor materials in bulk-heterojunction solar cells. The terminal substitution pattern of the squaraines is varied from cyclic over linear to branched including a stereogenic center.

Evidence of aquaporin involvement in human central pontine myelinolysis.

Background: Central pontine myelinolysis (CPM) is a demyelinating disorder of the central basis pontis that is often associated with osmotic stress. The aquaporin water channels (AQPs) have been pathogenically implicated because serum osmolarity changes redistribute water and osmolytes among various central nervous system compartments.

Results: We characterized the immunoreactivity of aquaporin-1 and aquaporin-4 (AQP1 and AQP4) and associated neuropathology in microscopic transverse sections from archival autopsied pontine tissue from 6 patients with pathologically confirmed CPM.

Staging TDP-43 pathology in Alzheimer's disease.

TDP-43 immunoreactivity occurs in 19-57 % of Alzheimer's disease (AD) cases. Two patterns of TDP-43 deposition in AD have been described involving hippocampus (limbic) or hippocampus and neocortex (diffuse), although focal amygdala involvement has been observed. In 195 AD cases with TDP-43, we investigated regional TDP-43 immunoreactivity with the aim of developing a TDP-43 in AD staging scheme.

Nonamnestic mild cognitive impairment progresses to dementia with Lewy bodies.

Objective: To determine the rate of progression of mild cognitive impairment (MCI) to dementia with Lewy bodies (DLB).

Methods: We followed 337 patients with MCI in the Mayo Alzheimer's Disease Research Center (range 2-12 years). Competing risks survival models were used to examine the rates of progression to clinically probable DLB and Alzheimer disease (AD).

Natalizumab-associated progressive multifocal leukoencephalopathy in a patient with multiple sclerosis: a postmortem study.

Natalizumab, a monoclonal antibody directed against α4 integrins, has, to date, been associated with 399 cases of progressive multifocal leukoencephalopathy (PML) worldwide in patients receiving treatment for multiple sclerosis (MS). Because of the limited number of histologic studies, the possible interplay between MS and PML lesions has not been investigated. We report the clinical, radiologic, and histologic findings of an MS patient who developed PML after 32 months of natalizumab monotherapy.

Novel mutation in MAPT exon 13 (p.N410H) causes corticobasal degeneration.

In order to determine the frequency of microtubule-associated protein tau gene (MAPT) mutations and rare variants in CBD, we performed a systematic sequence analysis of MAPT coding and 3′ untranslated region (3′UTR) in a large cohort of autopsy-confirmed CBD patients (N = 109). This identified a novel MAPT mutation in exon 13, p.N410H, in a case that is neuropathologically indistinguishable from sporadic CBD.

MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies.

Objective: To determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy.

Methods: Patients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry.

Neurocognitive speed associates with frontotemporal lobar degeneration TDP-43 subtypes.

Frontotemporal lobar degeneration (FTLD) is pathologically heterogeneous with the TAR DNA binding protein 43 kDa (TDP-43) proteinopathy the most common substrate. Previous work has identified atrophy patterns across TDP-43 subtypes with Type A showing greater frontotemporal and parietal atrophy, Type C predominantly anterior temporal, and Type B predominantly posterior frontal. Despite neuroanatomical correlates of involvement, neuropsychological findings have been inconsistent.

Diffuse anaplastic leptomeningeal oligodendrogliomatosis mimicking neurosarcoidosis.

Diffuse leptomeningeal oligodendrogliomatosis is a rare, frequently fatal CNS malignancy that most often affects children. Although potentially treatable with chemotherapy and radiation, the radiologic findings are nonspecific and pathologic confirmation of the diagnosis is difficult. We describe an adult patient whose initial presentation mimicked neurosarcoidosis.

Risk factors for dementia with Lewy bodies: a case-control study.

Objective: To determine the risk factors associated with dementia with Lewy bodies (DLB).

Methods: We identified 147 subjects with DLB and sampled 2 sex- and age-matched cognitively normal control subjects for each case. We also identified an unmatched comparison group of 236 subjects with Alzheimer disease (AD).

Dissecting phenotypic traits linked to human resilience to Alzheimer's pathology.

Clinico-pathological correlation studies and positron emission tomography amyloid imaging studies have shown that some individuals can tolerate substantial amounts of Alzheimer's pathology in their brains without experiencing dementia. Few details are known about the neuropathological phenotype of these unique cases that might prove relevant to understanding human resilience to Alzheimer's pathology. We conducted detailed quantitative histopathological and biochemical assessments on brains from non-demented individuals before death whose brains were free of substantial Alzheimer's pathology, non-demented individuals before death but whose post-mortem examination demonstrated significant amounts of Alzheimer's changes ('mismatches'), and demented Alzheimer's cases.

Pituicytoma with gelsolin amyloid deposition.

Pituicytoma is a rare low-grade (WHO grade I) sellar region glioma. Among sellar tumors, pituitary adenomas, mainly prolactinomas, may show amyloid deposits. Gelsolin is a ubiquitous calcium-dependent protein that regulates actin filament dynamics.

Personality and cognitive decline in the Baltimore Epidemiologic Catchment Area follow-up study.

Objective: To determine the association between personality domains and 11-year cognitive decline in a sample from a population-based study.

Method: Data from Waves 3 (1993-1996) and 4 (2003-2004) of the Baltimore cohort of the Epidemiologic Catchment Area (ECA) study were used for analyses. The sample included 561 adults (mean age ± SD: 45.

Midbrain atrophy is not a biomarker of progressive supranuclear palsy pathology.

Background And Purpose: Midbrain atrophy is a characteristic feature of progressive supranuclear palsy (PSP), although it is unclear whether it is associated with the PSP syndrome (PSPS) or PSP pathology. The aim of the present study was to determine whether midbrain atrophy is a useful biomarker of PSP pathology, or whether it is only associated with typical PSPS.

Methods: All autopsy-confirmed subjects were identified with the PSP clinical phenotype (i.

Parabrachial nucleus involvement in multiple system atrophy.

Unlabelled: Multiple system atrophy (MSA) is associated with respiratory dysfunction, including sleep apnea, respiratory dysrhythmia, and laryngeal stridor. Neurons of the parabrachial nucleus (PBN) control respiratory rhythmogenesis and airway resistance.

Objectives: The objective of this study is to determine whether there was involvement of putative respiratory regions of the PBN in MSA.

Quantitative neurofibrillary tangle density and brain volumetric MRI analyses in Alzheimer's disease presenting as logopenic progressive aphasia.

Neurofibrillary tangles (NFTs) are one of the key histological lesions of Alzheimer's disease (AD) and are associated with brain atrophy. We assessed regional NFT density in 30 patients with AD, 10 of which presented as the logopenic variant of primary progressive aphasia (lvPPA) and 20 that presented as dementia of the Alzheimer's type (DAT). Regional grey matter volumes were measured using antemortem MRI.

Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder.

Objective: To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder.

Methods: The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria.

In situ synthesis of silver nanoparticle decorated vertical nanowalls in a microfluidic device for ultrasensitive in-channel SERS sensing.

A microfluidic device with integrated novel silver nanoparticle (Ag NPs) decorated nanowall structures was fabricated via in situ electrodeposition of Cu-core/C-sheath nanowalls, followed by a facile in-channel silver galvanic replacement reaction method at room temperature. The integrated microfluidic devices with Ag NPs decorated nanowalls, serving as a highly active Raman substrate, were then applied for in-channel surface-enhanced Raman scattering (SERS) sensing using crystal violet as the model compound. The results show that the presence of a PDMS microfluidic channel does not significantly affect the Raman signal and crystal violet as low as 50 pM is prominently detected.