Search results for "amyloid"
showing 10 items of 494 documents
P3‐271: Presenilin‐1 (PS1) and amyloid precursor protein (APP) mutations present in mouse models of Alzheimer's disease in their response to γ‐secret…
2009
P3‐039: Axonal neuritic pathology induces early presynaptic alterations in ps1/APP Alzheimer's mice hippocampus
2011
Loss of neurons in the hippocampus correlates with memory impairment in AD. Significant early reduction in the numerical density of hippocampal SOM interneurons was found in single (APPswe) and double (APPswe/ PS1dE9 and APPswe/TauP301S-G272V) transgenic models based on APP over expression and amyloid production. However, this inhibitory population was unaffected in age-matched single PS1 and tau transgenic mice as well as nontransgenic controls. Whereas SOM neuron loss in APPswe/PS1dE9 was associated to the onset of extracellular amyloid pathology in double APP/ tau mice this loss preceded plaque formation. Conclusions: As in human AD, somatostatin cell loss is a common early pathological …
Obstructive sleep apnea and Alzheimer’s disease-related cerebrospinal fluid biomarkers in mild cognitive impairment
2020
Abstract Previous studies have demonstrated that sleep-breathing disorders, and especially obstructive sleep apnea (OSA), can be observed in patients with a higher risk of progression to Alzheimer’s disease (AD). Recent evidence indicates that cerebrospinal fluid (CSF) AD-biomarkers are associated with OSA. In this study, we investigated these associations in a sample of patients with mild cognitive impairment (MCI), a condition that is considered the first clinical phase of AD, when patients showed biomarkers consistent with AD pathology. A total of 57 patients (mean age = 66.19; SD = 7.13) with MCI were included in the study. An overnight polysomnography recording was used to assess objec…
Protective Effects of L- and D-Carnosine on R-Crystallin Amyloid Fibril Formation: Implications for Cataract Disease
2009
Mildly denaturing conditions induce bovine ?-crystallin, the major structural lens protein, to self-assemble into fibrillar structures in vitro. The natural dipeptide L-carnosine has been shown to have potential protective and therapeutic significance in many diseases. Carnosine derivatives have been proposed as potent agents for ophthalmic therapies of senile cataracts and diabetic ocular complications. Here we report the inhibitory effect induced by the peptide (L- and D-enantiomeric form) on ?-crystallin fibrillation and the almost complete restoration of the chaperone activity lost after denaturant and/or heat stress. Scanning force microscopy (SFM), thioflavin T, and a turbidimetry ass…
Disentangling the Amyloid Pathways: A Mechanistic Approach to Etiology
2020
Amyloids are fibrillar protein aggregates associated with diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), type II diabetes and Creutzfeldt–Jakob disease. The process of amyloid polymerization involves three pathological protein transformations; from natively folded conformation to the cross-β conformation, from biophysically soluble to insoluble, and from biologically functional to non-functional. While amyloids share a similar cross-β conformation, the biophysical transformation can either take place spontaneously via a homogeneous nucleation mechanism (HON) or catalytically on an exogenous surface via a heterogeneous nucleation mechanism (HEN). Here, we postulate that…
Amyloid in Alzheimer’s Disease: Guilty Beyond Reasonable Doubt?
2017
Recently failed antiamyloidogenic trials call for an objective reassessment of the dominating amyloid cascade hypothesis of Alzheimer's disease (AD). Ongoing efforts focusing on amyloid β protein (Aβ), its deposition, and its removal need to be complemented by more intensive research in new directions. Those may either integrate amyloid pathology or will propose pathogenetic routes independent of Aβ in the search for the causes of AD.
ADAM10 in Alzheimer's disease: Pharmacological modulation by natural compounds and its role as a peripheral marker.
2019
Abstract Alzheimer’s disease (AD) represents a global burden in the economics of healthcare systems. Amyloid-β (Aβ) peptides are formed by amyloid-β precursor protein (AβPP) cleavage, which can be processed by two pathways. The cleavage by the α-secretase A Disintegrin And Metalloprotease 10 (ADAM10) releases the soluble portion (sAβPPα) and prevents senile plaques. This pathway remains largely unknown and ignored, mainly regarding pharmacological approaches that may act via different signaling cascades and thus stimulate non-amyloidogenic cleavage through ADAM10. This review emphasizes the effects of natural compounds on ADAM10 modulation, which eventuates in a neuroprotective mechanism. M…
Why Women Have More Alzheimer's Disease Than Men: Gender and Mitochondrial Toxicity of Amyloid-β Peptide
2010
The main risk factors for developing Alzheimer's disease (AD) are age and gender. The incidence of the disease is higher in women than in men, and this cannot simply be attributed to the higher longevity of women versus men. Thus, there must be a specific pathogenic mechanism to explain the higher incidence of AD cases in women. In this regard, it is notable that mitochondria from young females are protected against amyloid-beta toxicity, generate less reactive oxygen species, and release less apoptogenic signals than those from males. However, all this advantage is lost in mitochondria from old females. Since estrogenic compounds protect against mitochondrial toxicity of amyloid-beta, estr…
The Blood-Brain Barrier in Alzheimer’s Disease
2020
The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is one of the characteristic hallmarks of Alzheimer's disease (AD). Aβ-peptide brain homeostasis is governed by its production and various clearance mechanisms. The blood-brain barrier provides a large surface area for influx and efflux mechanisms into and out of the brain. Different transporters and receptors have been implicated to play crucial roles in Aβ clearance from brain. Besides Aβ transport, the blood-brain barrier tightly regulates the brain's microenvironment; however, vascular alterations have been shown in patients with AD. Here, we summarize how the blood-brain barrier changes during aging and in disease and focus …