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Article
Clinical and biochemical correlates of insoluble α-synuclein in dementia with Lewy bodies
α-Synuclein is a major constituent of Lewy bodies, the fibrillar aggregates that form within neurons in Parkinson’s disease and dementia with Lewy bodies (DLB). Recent biochemical data show that α-synuclein ac...
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Article
No alteration in tau exon 10 alternative splicing in tangle-bearing neurons of the Alzheimer’s disease brain
Defective splicing of tau mRNA, promoting a shift between tau isoforms with (4R tau) and without (3R tau) exon 10, is believed to be a pathological consequence of certain tau mutations causing frontotemporal d...
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Article
Association study of cholesterol-related genes in Alzheimer’s disease
Alzheimer’s disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have...
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Article
Increase in the relative expression of tau with four microtubule binding repeat regions in frontotemporal lobar degeneration and progressive supranuclear palsy brains
Some cases of familial frontotemporal dementia (FTD) leading to frontotemporal lobar degeneration (FTLD) are caused by mutations in tau on chromosome 17 (FTDP-17). Certain mutations alter the ratio between four (...
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Article
Frontotemporal dementia in a large Swedish family is caused by a progranulin null mutation
Mutations in the progranulin (PGRN) gene have recently been identified in families with frontotemporal lobar degeneration and ubiquitin-positive brain inclusions linked to chromosome 17q21. We have previously des...
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Article
Open AccessPyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases
The presence of AβpE3 (N-terminal truncated Aβ starting with pyroglutamate) in Alzheimer’s disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of ...
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Article
Open AccessN-truncated Abeta starting with position four: early intraneuronal accumulation and rescue of toxicity using NT4X-167, a novel monoclonal antibody
The amyloid hypothesis in Alzheimer disease (AD) considers amyloid β peptide (Aβ) deposition causative in triggering down-stream events like neurofibrillary tangles, cell loss, vascular damage and memory decli...
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Article
Open AccessThe Arctic AβPP mutation leads to Alzheimer’s disease pathology with highly variable topographic deposition of differentially truncated Aβ
The Arctic mutation (p.E693G/p.E22G)fs within the β-amyloid (Aβ) region of the β-amyloid precursor protein gene causes an autosomal dominant disease with clinical picture of typical Alzheimer’s disease. Here w...
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Article
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease
Philippe Amouyel, Julie Williams, Gerard Schellenberg, Sudha Seshadri and colleagues report a meta-analysis of genome-wide association studies for late-onset Alzheimer's disease in 17,008 cases and 37,154 cont...
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Open AccessAbundance of Aβ5-xlike immunoreactivity in transgenic 5XFAD, APP/PS1KI and 3xTG mice, sporadic and familial Alzheimer’s disease
According to the modified amyloid hypothesis the main event in the pathogenesis of Alzheimer’s disease (AD) is the deposition of neurotoxic amyloid β-peptide (Aβ) within neurons. Additionally to full-length pe...
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Article
Micellar extraction possesses a new advantage for the analysis of Alzheimer’s disease brain proteome
Integral membrane proteins (MPs), such as transporters, receptors, and ion channels, are of great interest because of their participation in various vital cellular functions including cell–cell interactions, i...
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Open AccessDeposition of C-terminally truncated Aβ species Aβ37 and Aβ39 in Alzheimer’s disease and transgenic mouse models
In Alzheimer’s disease (AD) a variety of amyloid β-peptides (Aβ) are deposited in the form of extracellular diffuse and neuritic plaques (NP), as well as within the vasculature. The generation of Aβ from its p...
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Article
α-Synuclein in Extracellular Vesicles: Functional Implications and Diagnostic Opportunities
Fibrillar inclusions of intraneuronal α-synuclein can be detected in certain brain areas from patients with Parkinson’s disease (PD) and other disorders with Lewy body pathology. These insoluble protein aggreg...
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Article
Open AccessHigh tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer’s disease
Increased concentrations of cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau, as well as decreased amyloid-β 42 peptide, are biomarkers of Alzheimer’s disease (AD) pathology, but few studies ...
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Article
Cellular Uptake of α-Synuclein Oligomer-Selective Antibodies is Enhanced by the Extracellular Presence of α-Synuclein and Mediated via Fcγ Receptors
Immunotherapy targeting aggregated α-synuclein has emerged as a potential treatment strategy against Parkinson’s disease and other α-synucleinopathies. We have developed α-synuclein oligomer/protofibril select...
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Article
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and p...
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Article
Open AccessMap** of Surface-Exposed Epitopes of In Vitro and In Vivo Aggregated Species of Alpha-Synuclein
Aggregated alpha-synuclein is the main component of Lewy bodies, intraneuronal deposits observed in Parkinson’s disease and dementia with Lewy bodies. The objective of the study was to identify surface-exposed...
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Article
Open AccessAlpha-synuclein oligomer-selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha-synuclein exposed astrocytes
Due to its neurotoxic properties, oligomeric alpha-synuclein (α-syn) has been suggested as an attractive target for passive immunization against Parkinson’s disease (PD). In mouse models of PD, antibody treatm...
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Protocol
Generation and Characterization of Stable α-Synuclein Oligomers
Alpha-synuclein oligomers are linked to the pathogenesis of Parkinson’s disease and related neurodegenerative diseases. In this chapter, we present a method to generate kinetically stable α-synuclein oligomers...