Statistical methods for linking material composition to recombination losses in optoelectronic devices.

In light of the accumulation of characterization measurement data in the industrial production of solar cell devices, the investigation of a large amount of samples by statistical means lends itself to be a useful tool to gain further insights into how the data correlate with performance parameters. However, due to the multicollinearity among high-dimensional input parameters of compositional data, revealing the underlying patterns may prove to be a difficult endeavor. In this work, we present statistics consisting of 280 thin-film solar cell samples based on Cu(In, Ga)(S, Se)2 absorber layers whose depth-resolved composition was assessed by glow-discharge optical emission spectroscopy (GDOES). After parameterization of the features of [Ga]/([Ga] + [In])and[S]/([S] + [Se]) gradings, we employ two-way clustering in order to group samples and features by their similarity. In addition, using principal component analysis, information in the dataset, which is irrelevant to the problem, is removed by dimensionality reduction. In this way, it is possible to create a map that provides an overview of the GDOES data of all samples in their entirety, including correlations among features. More importantly, it also opens up a more precise way to plan further improvements in the compositional gradings by unveiling a path along which the experimenter can read the feature changes concerned with an improvement in the open-circuit voltage deficit or any other target parameter of interest. New samples can then be assigned to existing cluster centroids to predict what target parameter value they would assume.

Bioglass/collagen scaffolds combined with bone marrow stromal cells on bone healing in an experimental model in cranial defects in rats.

This study aimed to develop bone regenerative therapeutic strategies, based on the addition of bone marrow stromal cells (BMSC) on bioglass/collagen (BG/COL) scaffolds. For this purpose, an in vivo study was conducted using tissue response of the BG/COL scaffolds combined with BMSC in a critical-size defects. Wistar rats were submitted to the surgical procedure to perform the cranial critical size bone defects and distributed in four groups (20 animals per group): Control Group (CG) (rats submitted to the cranial bone defect surgery without treatment), Bioglass Group (BG) (rats treated with BG), BG/COL Group (rats treated with BG/COL) and Bioglass/Collagen and BMSC Group (BG/COL/BMSC) (rats treated with BG/COL scaffolds enriched with BMSCs). Animals were euthanized 15 and 30 days after surgery. Scanning electron microscopy, histopathological and immunohistochemistry analysis were used. SEM analysis demonstrated that porous scaffolds were obtained, and Col fibers were successfully impregnated to BG matrices. The implantation of the BMSC on BG/COL based scaffolds was effective in stimulating newly bone formation and produced an increased immunoexpression of markers related to the bone repair. These results highlight the potential of BG/COL scaffolds and BMSCs to be used as a therapeutic approach for bone regeneration.

Marine collagen scaffolds and photobiomodulation on bone healing process in a model of calvaria defects.

INTRODUCTION: Collagen from marine esponges has been used as a promising material for tissue engineering proposals. Similarly, photobiomodulation (PBM) is able of modulating inflammatory processes after an injury, accelerating soft and hard tissue healing and stimulating neoangiogenesis. However, the effects of the associated treatments on bone tissue healing have not been studied yet. In this context, the present study aimed to evaluate the biological temporal modifications (using two experimental periods) of marine sponge collagen or sponging (SPG) based scaffold and PBM on newly formed bone using a calvaria bone defect model. MATERIAL AND METHODS: Wistar rats were distributed into two groups: SPG or SPG/PBM and euthanized into two different experimental periods (15 and 45 days post-surgery). A cranial critical bone defect was used to evaluate the effects of the treatments. Histology, histomorfometry and immunohistological analysis were performed. RESULTS: Histological findings demonstrated that SPG/PBM-treated animals, 45 days post-surgery, demonstrated a higher amount of connective and newly formed bone tissue at the region of the defect compared to CG. Notwithstanding, no difference among groups were observed in the histomorphometry. Interestingly, for both anti-transforming growth factor-beta (TGF-ß) and anti-vascular endothelial growth factor (VEGF) immunostaining, higher values for SPG/PBM, at 45 days post-surgery could be observed. CONCLUSION: It can be concluded that the associated treatment can be considered as a promising therapeutical intervention.

Influence of the incorporation of marine spongin into a Biosilicate®: an in vitro study.

The combination of different biomaterials can be a promising intervention for the composites manufacture, mainly by adding functional and structural characteristics of each material and guarantee the advantages of the use of these composites. In this context, the aim of this study was to develop and evaluated the influence of the incorporation of marine spongin (SPG) into Biosilicate® (BS) in different proportions be used during bone repair. For this purpose, it was to develop and investigate different BS/SPG formulations for physico-chemical and morphological characteristics by pH, loss mass, Fourier transform infrared spectrometer (FTIR) and scanning electron microscope (SEM) analysis. Additionally, the influence of these composites on cell viability, proliferation, and alkaline phosphatase (ALP) activity were investigated. The results revealed that the pH values of all BS groups (with or without SPG) increased over time. A significant mass loss was observed in all composites, mainly with higher SPG percentages. Additionaly, SEM micrographies demonstrated fibers of SPG into BS and material degradation over time. Moreover, FTIR spectral analysis revealed characteristic peaks of PMMA, BS, and SPG in BS/SPG composites. BS/SPG groups demonstrated a positive effect for fibroblast proliferation after 3 and 7 days of culture. Additionally, BS and BS/SPG formulations (at 10% and 20% of SPG) presented similar values of osteoblasts viability and proliferation after 7 days of culture. Furthermore, ALP activity demonstrated no significant difference between BS and BS/SPG scaffolds, at any composition. Based on the present in vitro results, it can be concluded that the incorporation of SPG into BS was possible and produced an improvement in the physical-chemical characteristics and in the biological performance of the graft especially the formulation with 80/20 and 90/10. Future research should focus on in vivo evaluations of this novel composite.

Incorporation of Collagen from Marine Sponges (Spongin) into Hydroxyapatite Samples: Characterization and In Vitro Biological Evaluation.

Biomaterial-based bone grafts have an important role in the field of bone tissue engineering. One of the most promising classes of biomaterials is collagen, including the ones from marine biodiversity (in general, called spongin (SPG)). Also, hydroxyapatite (HA) has an important role in stimulating bone metabolism. Therefore, this work investigated the association of HA and SPG composites in order to evaluate their physico-chemical and morphological characteristics and their in vitro biological performance. For this, pre-set composite disks were evaluated by means of mass loss after incubation, pH, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and "in vitro" cell viability. pH measurements showed no statistical difference between groups. Moreover, a higher mass loss was observed for HA/SPG70/30 compared to the other groups for all experimental periods. Moreover, SEM representative micrographs showed the degradation of the samples with and without immersion. FTIR analysis demonstrated the absorption peaks for poly(methyl methacrylate) (PMMA), HA, and SPG. A higher L292 cell viability for control and PMMA was observed compared to HA and HA/SPG 90/10. Also, HA/SPG 70/30 showed higher cell viability compared to HA and HA/SPG 90/10 on days 3 and 7 days of culture. Furthermore, HA showed a significant lower MC3T3 cell viability compared to control and HA/SPG 70/30 on day 3 and no significant difference was observed between the composites in the last experimental period. Based on our investigations, it can be concluded that the mentioned composites were successfully obtained, presenting improved biological properties, especially the one mimicking the composition of bone (with 70% of HA and 30% of SPG). Consequently, these data highlight the potential of the introduction of SPG into HA to improve the performance of the graft for bone regeneration applications. Further long-term studies should be carried out to provide additional information concerning the late stages of material degradation and bone healing in the presence of HA/SPG.

A cavernous sinus lesion clinically responsive to steroids.

Tolosa Hunt syndrome (THS) is characterized by painful ophthalmoplegia secondary to idiopathic granulomatous inflammation of the cavernous sinus. The characteristic finding on MRI is an enhancing T1 isointense and T2 hypo- or hyperintense cavernous sinus mass lesion, which may result in focal narrowing of the ipsilateral internal carotid artery. Although the incidence is quite rare, it is a common diagnostic consideration in cases that present with multiple cranial neuropathies. However, the differential diagnosis for a unilateral cavernous sinus lesion in adults is broad and includes neoplastic, inflammatory (such as sarcoidosis and immunoglobulin G4-related disease [IgG4-RD]), infectious etiologies (such as syphilis and leprosy), as well as vascular lesions. We describe a patient presenting with neurologic symptoms referable to a persistent unilateral cavernous sinus MRI abnormality, initially thought to be consistent with Tolosa-Hunt syndrome, that was clinically but not radiographically responsive to steroids. Following reevaluation due to the presence of new symptoms, pathology revealed that the abnormality was most consistent with chordoma, a rare skull based tumor. In patients with a presumed diagnosis of Tolosa-Hunt syndrome, close clinical and radiographic follow-up is imperative, with early consideration for biopsy in patients that fail to respond to treatment both clinically and radiographically.

Biosilicate/PLGA osteogenic effects modulated by laser therapy: In vitro and in vivo studies.

The main purpose of the present work was to evaluate if low laser level therapy (LLLT) can improve the effects of Biosilicate®/PLGA (BS/PLGA) composites on cell viability and bone consolidation using a tibial defects of rats. The composites were characterized by scanning electron microscope (SEM) and reflection Fourier transform infrared spectrometer (FTIR). For the in vitro study, fibroblast and osteoblast cells were seeded in the extract of the composites irradiated or not with LLLT (Ga-Al-As, 808nm, 10J/cm2) to assess cell viability after 24, 48 and 72h. For the in vivo study, 80 Wistar rats with tibial bone defects were distributed into 4 groups (BS; BS+LLLT; BS/PLGA and BS/PLGA+LLLT) and euthanized after 2 and 6weeks. Laser irradiation Ga-Al-As (808nm, 30J/cm2) in the rats was performed 3 times a week. The SEM and FTIR results revealed that PLGA were successfully inserted into BS and the microparticles degraded over time. The in vitro findings demonstrated higher fibroblast viability in both BS/PLGA groups after 24h and higher osteoblast viability in BS/PLGA+LLLT in all periods. As a conclusion, animals treated with BS/PLGA+LLLT demonstrated an improved material degradation and an increased amount of granulation tissue and newly formed bone.

Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) due to microtubule-associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy.

AIM: The p.P301L mutation in microtubule-associated protein tau (MAPT) is a common cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We compare clinicopathologic features of five unrelated and three related (brother, sister and cousin) patients with FTDP-17 due to p.P301L mutation. METHODS: Genealogical, clinical, neuropathologic and genetic data were reviewed from eight individuals. RESULTS: The series consisted of five men and three women with an average age of death of 58 years (52-65 years) and average disease duration of 9 years (3-14 years). The first symptoms were those of behavioural variant frontotemporal dementia in seven patients and semantic variant of primary progressive aphasia in one. Three patients were homozygous for the MAPT H1 haplotype; five had H1/H2 genotype. The apolipoprotein E genotype was ϵ3/ϵ3 in seven and ϵ3/ϵ4 in one. The average brain weight was 1015 g (876-1188 g). All had frontotemporal lobar or more diffuse cortical atrophy. Except for one patient, the hippocampus and parahippocampal gyrus had minimal atrophy, whereas there was atrophy of middle and inferior temporal gyri. Dentate fascia neuronal dispersion was identified in three patients, two of whom had epilepsy. In one patient there was extensive white matter tau involvement with Gallyas-positive globular glial inclusions typical of globular glial tauopathy (GGT). CONCLUSIONS: This clinicopathologic study shows inter- and intra-familial clinicopathologic heterogeneity of FTDP-17 due to MAPT p.P301L mutation, including GGT in one patient.

Blocking of injected holes at the charge extracting interface.

For an organic crystal with four metal electrodes, we have investigated the charge transfer between the injecting electrode 1 and the extracting electrodes 2-4. Each of the measured I-V curves was decomposed into three components, characterizing the injecting and extracting interfaces, and the squaraine (SQ) crystal. We considered a case, where the resistance of the organic crystal was significantly smaller than that of the interfaces. The different values of the contact resistances measured at different electrodes are related to differing values of the barrier height [Formula: see text] and its width d, which were determined using the Simmons approximation. When the extracting interface has a larger contact resistance compared to that of the SQ crystal and that of the injecting interface, part of the injected holes remains located within the SQ crystal. The voltage V 0, at which the injected hole density begins to exceed the extracted hole density within the SQ crystal, depends on the ratio [Formula: see text] (indices ex and in describe the extracting and injecting electrodes, respectively). The smaller δ is, the larger is voltage V 0.

Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings.

BACKGROUND AND OBJECTIVES: We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. METHODS AND RESULTS: Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. CONCLUSIONS: Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry.

DNAJC13 p.Asn855Ser mutation screening in Parkinson's disease and pathologically confirmed Lewy body disease patients.

BACKGROUND: Recently, a novel mutation in exon 24 of DNAJC13 gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi-incident Mennonite family. METHODS: In the present study the mutation containing exon of the DNAJC13 gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD). RESULTS: Our sequence analysis did not identify any coding variants in exon 24 of DNAJC13. Two previously described variants in intron 23 (rs200204728 and rs2369796) were observed. CONCLUSION: Our results indicate that the region surrounding the DNAJC13 p.Asn855Ser substitution is highly conserved and mutations in this exon are not a common cause of PD or LBD among Caucasian populations.

Putative neuropathological interactions in MSA: focus in the rostral ventrolateral medulla.

We used double immunocytochemistry for α-synuclein and markers of sympathoexcitatory neurons, oligodendrocytes, iron metabolism, and autophagy to study putative neuropathological interactions in multiple system atrophy. We focused in the rostral ventrolateral medulla as a prototype vulnerable region. We found that loss of C1 neurons and oligodendrocytes related to glial cytoplasmic inclusion accumulation, downregulation of iron transport, and upregulation of autophagy and ferritin expression in these area.

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. Single crystal structures are determined, and, in the case of chiral squaraine, unusual formation of stereoisomer co-crystals is revealed. The thin film absorbance spectra show characteristic signatures of H- and J-bands or hint at the formation of tautomers. The general feasibility of these model compounds for photovoltaic applications is studied by light-induced electron spin resonance spectroscopy. The impact of the different molecular substitution patterns on aggregation behavior and, consequently, their optoelectronic solid state properties including charge carrier mobility and finally the solar cell performance are investigated.

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.e. PSPS) or PSP pathology and a volumetric MRI. Of 24 subjects with PSP pathology, 11 had a clinical diagnosis of PSPS (PSP-PSPS), and 13 had a non-PSPS clinical diagnosis (PSP-other). Three subjects had PSPS and corticobasal degeneration pathology (CBD-PSPS). Healthy control and disease control groups (i.e. a group without PSPS or PSP pathology) and a group with CBD pathology and corticobasal syndrome (CBD-CBS) were selected. The midbrain area was measured in all subjects. [Correction added on 21 June 2013, after first online publication: the abbreviation of corticobasal degeneration pathology was changed from CBD-PSP to CBD-PSPS.] RESULTS: The midbrain area was reduced in each group with clinical PSPS (with and without PSP pathology). The group with PSP pathology and non-PSPS clinical syndromes did not show reduced midbrain area. Midbrain area was smaller in the subjects with PSPS than in those without PSPS (P < 0.0001), with an area under the receiver operator curve of 0.99 (0.88, 0.99). A midbrain area cut-point of 92 mm(2) provided optimum sensitivity (93%) and specificity (89%) for differentiation. CONCLUSION: Midbrain atrophy is associated with the clinical presentation of PSPS, but not with the pathological diagnosis of PSP in the absence of clinical PSPS. This finding has important implications for the utility of midbrain measurements as diagnostic biomarkers for PSP pathology.

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. METHODS: We examined the pons at autopsy in 10 cases with neuropathologically confirmed MSA and 8 age-matched controls. Sections obtained throughout the pons were processed for calcitonin-gene related peptide (CGRP) and Nissl staining to identify the lateral crescent of the lateral PBN (LPB) and the Kölliker-Fuse nucleus (K-F), which are involved in respiratory control. Cell counts were performed using stereology. RESULTS: There was loss of CGRP neurons in the PBN in MSA (total estimated cell counts for the external LPB cluster was 12,584 ± 1146 in controls and 5917 ± 389 in MSA, p<0.0001); for the external medial PBN (MPB) cluster it was 15,081 ± 1758 in controls and 7842 ± 466 in MSA, p<0.001. There was also neuronal loss in putative respiratory regions of the PBN, including the lateral crescent of the LPB (13,039 ± 1326 in controls and 4164 ± 872 in MSA, p<0.0001); and K-F (5120 ± 495 in controls and 999 ± 308 in MSA, p<0.0001). CONCLUSIONS: There is involvement of both CGRP and putative respiratory cell groups in the PBN in MSA. Whereas the clinical implications of CGRP cell loss are still undetermined, involvement of the LPB and K-F may contribute to respiratory dysfunction in this disorder.

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. RESULTS: 172 cases were identified, of whom 143 (83%) were men. The mean±SD age of onset in years for the core features were as follows - RBD, 62±14 (range, 20-93), cognitive impairment (n=147); 69±10 (range, 22-90), parkinsonism (n=151); 68±9 (range, 20-92), and autonomic dysfunction (n=42); 62±12 (range, 23-81). Death age was 75±9 years (range, 24-96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10±12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n=97), Parkinson's disease with or without mild cognitive impairment or dementia (n=32), multiple system atrophy (MSA) (n=19), Alzheimer's disease (AD)(n=9) and other various disorders including secondary narcolepsy (n=2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n=1). The neuropathologic diagnoses were Lewy body disease (LBD)(n=77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n=59), MSA (n=19), AD (n=6), progressive supranulear palsy (PSP) (n=2), other mixed neurodegenerative pathologies (n=6), NBIA-1/LBD/tauopathy (n=1), and hypothalamic structural lesions (n=2). Among the neurodegenerative disorders associated with RBD (n=170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features. CONCLUSIONS: In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.

Diffusion-weighted imaging characteristics of biopsy-proven demyelinating brain lesions.

OBJECTIVES: To describe lesional diffusion-weighted imaging characteristics in a cohort of patients with biopsy-proven CNS inflammatory demyelinating disease (IDD) and compare diffusion characteristics of ring-enhancing CNS IDD lesions vs abscesses and tumors. METHODS: Forty prebiopsy apparent diffusion coefficient (ADC) maps were reviewed from 30 patients with CNS IDD. Lesions were analyzed for size, T2-weighted (T2W) hypointense rim, enhancement, and ADC pattern. ADC patterns of CNS IDD ring-enhancing lesions were compared with a published cohort of 35 patients with ring-enhancing tumors and abscesses. RESULTS: IDD lesions displayed a spectrum of peripheral ADC patterns at the lesion edge: restricted diffusion (low ADC), 33%; increased diffusion (high ADC), 60%; and normal diffusion (homogeneously isointense), 7%. Of biopsied lesions, 93% enhanced (ring, 52%; heterogeneous, 34%; homogeneous, 7%). A hypointense T2W rim was observed in 53%. A ring pattern on ADC (isointense or dark) was associated with T2W hypointense rims (p = 0.02) but not with ring enhancement. On serial imaging, 4 of 7 (57%) patients demonstrated changes in ADC patterns. Peripheral restriction was more common in IDD (p = 0.006) than in tumors or abscesses, whereas central restriction was only observed in abscesses. Restricted lesions in the same stage were more common in the non-IDD cohort (42% vs 20%), with a uniform restricted pattern seen only in abscesses. CONCLUSIONS: In ring-enhancing lesions, peripheral diffusion restriction is more common in IDD than in tumors/abscesses, whereas central restriction is more common among abscesses. Rapid ADC pattern changes in IDD probably reflect dynamic lesion evolution and may distinguish IDD from tumors.

Neuropathological analysis of brainstem cholinergic and catecholaminergic nuclei in relation to rapid eye movement (REM) sleep behaviour disorder.

AIMS: Rapid eye movement sleep behaviour disorder (RBD) is characterized by loss of muscle atonia during rapid eye movement sleep and is associated with dream enactment behaviour. RBD is often associated with α-synuclein pathology, and we examined if there is a relationship of RBD with cholinergic neuronal loss in the pedunculopontine/laterodorsal tegmental nucleus (PPN/LDT), compared to catecholaminergic neurones in a neighbouring nucleus, the locus coeruleus (LC). METHODS: This retrospective study utilized human brain banked tissues of 11 Lewy body disease (LBD) cases with RBD, 10 LBD without RBD, 19 Alzheimer's disease (AD) and 10 neurologically normal controls. Tissues were stained with choline acetyl transferase immunohistochemistry to label neurones of PPN/LDT and tyrosine hydroxylase for the LC. The burden of tau and α-synuclein pathology was measured in the same regions with immunohistochemistry. RESULTS: Both the LC and PPN/LDT were vulnerable to α-synuclein pathology in LBD and tau pathology in AD, but significant neuronal loss was only detected in these nuclei in LBD. Greater cholinergic depletion was found in both LBD groups, regardless of RBD status, when compared with normals and AD. There were no differences in either degree of neuronal loss or burden of α-synuclein pathology in LBD with and without RBD. CONCLUSIONS: Whether decreases in brainstem cholinergic neurones in LBD contribute to RBD is uncertain, but our findings indicate these neurones are highly vulnerable to α-synuclein pathology in LBD and tau pathology in AD. The mechanism of selective α-synuclein-mediated neuronal loss in these nuclei remains to be determined.