Dementia is a decline in cognitive function that impairs a person's previous level of social and occupational function. Dementia is a very common medical condition that can result from diverse causes. Dementias are classified based on common clinical, genetic, and neuropathological features. The most common cause of dementia is Alzheimer's disease. Other major classes of disorders that cause demen

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

The aberrant accumulation of aggregated β-amyloid peptides (Aβ) as plaques is a hallmark of Alzheimer's disease (AD) neuropathology and reduction of Ab has become a leading direction of emerging experimental therapies for the disease. The mechanism(s) whereby Aβ is involved in the pathophysiology of the disease remain(s) poorly understood. Initially fibrils, and subsequently oligomers of extracell

Although β-amyloid (Aβ) plaques and tau neurofibrillary tangles are hallmarks of Alzheimer's disease (AD) neuropathology, loss of synapses is considered the best correlate of cognitive decline in AD, rather than plaques or tangles. How pathological Aβ and tau aggregation relate to each other and to alterations in synapses remains unclear. Since aberrant tau phosphorylation occurs in amyloid precur

A central question in Alzheimer's disease research is what role synaptic activity plays in the disease process. Synaptic activity has been shown to induce β-amyloid peptide release into the extracellular space, and extracellular β-amyloid has been shown to be toxic to synapses. We now provide evidence that the well established synaptotoxicity of extracellular β-amyloid requires β-secretase process

Immunotherapy against β-amyloid peptide (Aβ) is a leading therapeutic direction for Alzheimer disease (AD). Experimental studies in transgenic mouse models of AD have demonstrated that Aβ immunization reduces Aβ plaque pathology and improves cognitive function. However, the biological mechanisms by which Aβ antibodies reduce amyloid accumulation in the brain remain unclear. We provide evidence tha

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

Increasing evidence links intraneuronal β-amyloid (Aβ 42) accumulation with the pathogenesis of Alzheimer's disease (AD). In Aβ precursor protein (APP) mutant transgenic mice and in human AD brain, progressive intraneuronal accumulation of Aβ42 occurs especially in multivesicular bodies (MVBs). We hypothesized that this impairs the MVB sorting pathway. We used the trafficking of the epidermal grow

Synaptic dysfunction is increasingly viewed as an early manifestation of Alzheimer's disease (AD), but the cellular mechanism by which β-amyloid (Aβ) may affect synapses remains unclear. Since cultured neurons derived from APP mutant transgenic mice secrete elevated levels of Aβ and parallel the subcellular Aβ accumulation seen in vivo, we asked whether alterations in synapses occur in this settin

Amyloid-β peptide is elevated in the brains of patients with Alzheimer disease and is believed to be causative in the disease process. Amyloid-β reduces glutamatergic transmission and inhibits synaptic plasticity, although the underlying mechanisms are unknown. We found that application of amyloid-β promoted endocytosis of NMDA receptors in cortical neurons. In addition, neurons from a genetic mou

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

Intrinsic optical emissions, such as autofluorescence and second harmonic generation (SHG), are potentially useful for functional fluorescence imaging and biomedical disease diagnosis for neurodegenerative diseases such as Alzheimer's disease (AD). Here, using multiphoton and SHG microscopy, we identified sources of intrinsic emissions in ex vivo, acute brain slices from AD transgenic mouse models

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

A growing body of evidence suggests a relationship between oxidative stress and β-amyloid (Aβ) peptide accumulation, a hall-mark in the pathogenesis of Alzheimer's disease (AD). However, a direct causal relationship between oxidative stress and Aβ pathology has not been established in vivo. Therefore, we crossed mice with a knockout of one allele of manganese superoxide dismutase (MnSOD), a critic

Multiple lines of evidence implicate β-amyloid (Aβ) in the pathogenesis of Alzheimer's disease (AD), but the mechanisms whereby Aβ is involved remain unclear. Addition of Aβ to the extracellular space can be neurotoxic. Intraneuronal Aβ42 accumulation is also associated with neurodegeneration. We reported previously that in Tg2576 amyloid precursor protein mutant transgenic mice, brain Aβ42 locali

Molecular chaperones and their functions in protein folding have been implicated in several neurodegenerative diseases, including Parkinson's disease and Huntington's disease, which are characterized by accumulation of protein aggregates (e.g., α-synuclein and huntingtin, respectively). These aggregates have been shown in various experimental systems to respond to changes in levels of molecular ch

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

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.

Alzheimer's disease (AD) is characterized by the age-related deposition of β-amyloid (Aβ) 40/42 peptide aggregates in vulnerable brain regions. Multiple levels of evidence implicate a central role for Aβ in the pathophysiology of AD. Aβ peptides are generated by the regulated cleavage of an ≃700-aa Aβ precursor protein (βAPP). Full-length βAPP can undergo proteolytic cleavage either within the A β

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