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Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease

Background: The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase that plays a pivotal role in multiple fundamental biological processes, including synaptic plasticity. We explored the relationship between the mTOR pathway and β-amyloid (Ab)-induced synaptic dysfunction, which is considered to be critical in the pathogenesis of Alzheimer's disease (AD). Met

Av kärlek och plikt : Att bli familjehem till ett barnbarn, syskon eller syskonbarn

I denna avhandling står släktinghemsföräldrar i fokus och stor vikt har lagts vidderas erfarenheter av att ta hand om ett släktingbarn, något som sällanuppmärksammas i forskning kring släktingplacering. Det övergripande syftet med studien har varit att utifrån ett livsloppsperspektiv och med familjeteoretiska begrepp analysera vad det kan innebära att ta hand om en familjemedlems barn genom ett foThis dissertation focuses on kinship foster parents and their experiences caring for their kinship children, something that is rarely touched on in kinship care research. The primary purpose of this study is to, based on a life-course perspective and with family theoretical concepts, analyze what it might mean to take care of a family member’s child through a formal commitment such as a foster car

Intraneuronal Aβ accumulation and origin of plaques in Alzheimer's disease

Plaques are a defining neuropathological hallmark of Alzheimer's disease (AD) and the major constituent of plaques, the β-amyloid peptide (Aβ), is considered to play an important role in the pathophysiology of AD. But the biological origin of Aβ plaques and the mechanism whereby Aβ is involved in pathogenesis have been unknown. Aβ plaques were thought to form from the gradual accumulation and aggr

Immunocytochemical analysis of amyloid precursor protein and its derivatives

Histochemical analysis of postmortem human brains from subjects who suffered from dementia led to the discovery of Alzheimer’s disease a century ago. The histological lesions that characterized this common age-related dementia were the accumulation of senile plaques (SPs) and neurofibrillary tangles (NFTs). Subsequently, NFTs were found in a variety of degenerative diseases of the brain, while pla

Intraneuronal Alzheimer Aβ42 accumulates in multivesicular bodies and is associated with synaptic pathology

A central question in Alzheimer's disease concerns the mechanism by which β-amyloid contributes to neuropathology, and in particular whether intracellular versus extracellular β-amyloid plays a critical role. Alzheimer transgenic mouse studies demonstrate brain dysfunction, as β-amyloid levels rise, months before the appearance of β-amyloid plaques. We have now used immunoelectron microscopy to de

Intraneuronal Aβ42 accumulation in human brain

Alzheimer's disease (AD) is characterized by the deposition of senile plaques (SPs) and neurofibrillary tangles (NFTs) in vulnerable brain regions. SPs are composed of aggregated β-amyloid (Aβ) 40/42(43) peptides. Evidence implicates a central role for Aβ in the pathophysiology of AD. Mutations in βAPP and presenilin 1 (PS1) lead to elevated secretion of Aβ, especially the more amyloidogenic Aβ42.

Estrogen reduces neuronal generation of Alzheimer β-amyloid peptides

Alzheimer's disease (AD) is characterized by the accumulation of cerebral plaques composed of 40- and 42-amino acid ̄-amyloid (Aβ) peptides, and autosomal dominant forms of AD appear to cause disease by promoting brain Aβ accumulation. Recent studies indicate that postmenopausal estrogen replacement therapy may prevent or delay the onset of AD. Here we present evidence that physiological levels of

Amyloid-β oligomers are inefficiently measured by enzyme-linked immunosorbent assay

Amyloid-β (Aβ) peptide levels are widely measured by enzyme-linked immunosorbent assay (ELISA) in Alzheimer's disease research. Here, we show that oligomerization of Aβ results in underestimated Aβ ELISA levels. The implications are that comprehensive analysis of soluble Aβ requires either sample pretreatment at denaturing conditions or novel conformation-dependent immunoassays. Our findings might

Evidence for phosphorylation and oligomeric assembly of presenilin 1

Pathogenic mutations in presenilin 1 (PS1) are associated with ≃50% of early-onset familial Alzheimer disease. PS1 is endoproteolytically cleaved to yield a 30-kDa N-terminal fragment (NTF) and an 18-kDa C-terminal fragment (CTF). Using COS7 cells transfected with human PS1, we have found that phorbol 12,13-dibutyrate and forskolin increase the state of phosphorylation of serine residues of the hu

Alzheimer β-amyloid peptides : Normal and abnormal localization

Alzheimer's disease (AD) neuropathology is characterized by accumulation of "senile" plaques (SPs) and neurofibrillary tangles (NFTs) in vulnerable brain regions. SPs are principally composed of aggregates of up to 42/43 amino acid β-amyloid (Aβ) peptides. The discovery of familial AD (FAD) mutations in the genes for the amyloid precursor protein (APP) and presenilins (PSs), all of which increase

Immunotherapy for Alzheimer disease

Immunotherapy approaches for Alzheimer disease currently are among the leading therapeutic directions for the disease. Active and passive immunotherapy against the β-amyloid peptides that aggregate and accumulate in the brain of those afflicted by the disease have been shown by numerous groups to reduce plaque pathology and improve behavior in transgenic mouse models of the disease. Several ongoin

Current theories for the molecular and cellular pathogenesis of Alzheimer's disease

Over the past decade, the prevailing view for the molecular and cellular pathogenesis of Alzheimer's disease (AD) has centred on the β-amyloid (Aβ) peptide that accumulates in vulnerable brain areas in the disease. The amyloid cascade hypothesis postulates that the build up of Aβ in the brain causes damage to neurons, leading to dysfunction and loss of neurons, and the clinical phenotype of the am

Cellular and molecular basis of beta-amyloid precursor protein metabolism.

In molecular neurobiology, perhaps no molecule has been as thoroughly examined as Alzheimer's beta-amyloid precursor protein (beta-APP). In the years since the cDNA encoding beta-APP was cloned, the protein has been the subject of unparalleled scrutiny on all levels. From molecular genetics and cellular biology to neuroanatomy and epidemiology, no scientific discipline has been left unexplored - a

Myotonia in colchicine myoneuropathy

Colchicine may induce a myoneuropathy in patients with renal insufficiency. To date, myotonia has not been described in this disorder. We recently studied 4 patients treated with routine doses of colchicine who, in the setting of renal insufficiency, developed a severe myoneuropathy characterized by prominent myotonic discharges on electromyography. In addition, 1 of the 4 patients had profound cl

Mesencephalic clefts with associated eye movement disorders

Objective: To describe two patients with mesencephalic midline clefts and associated eye movement disorders. Design: Case reports. Results: The first patient developed bilateral internuclear ophthalmoplegia with exotropia, reduced convergence, right ptosis, right fourth-nerve palsy, and right elevator palsy several years after meningitis with hydrocephalus. The second patient had bilateral internu

Extraction and Modification of Macroalgal Polysaccharides for Current and Next-Generation Applications

Marine macroalgal (seaweed) polysaccharides are highly promising for next-generation applications in several industries. However, despite the reported comprehensive potential of these polysaccharides, commercial products are scarce on the market. Seaweed cultivations are increasing in number and production quantity, owing to an elevated global trend of utilization interest in seaweed. The extracti

Gene transfer across species boundaries in bryophytes : evidence from major life cycle stages in Homalothecium lutescens and H. sericeum

Background and Aims: The mosses Homalothecium lutescens and H. sericeum are genetically, morphologically and ecologically differentiated; mixed populations sometimes occur. In sympatric populations, intermediate character states among gametophytes and sporophytes have been observed, suggesting hybridization and introgression in such populations. Methods: We determined genotypes using bi-allelic co

Relational reference attribute grammars: Improving continuous model validation

Just like current software systems, conceptual models are characterised by increasing complexity and rate of change. Yet, these models only become useful if they can be continuously evaluated, validated and serialized. To achieve sufficiently low response times for large models, incremental analysis is required. Reference Attribute Grammars (RAGs) offer mechanisms to perform incremental analysis e

Ingrid Thulin

Artikel om Ingrid Thulin i Svenskt kvinnobiografiskt lexikon