Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer’s disease mouse models with abundant Aβ in plasma

2006 ◽  
Vol 24 (1) ◽  
pp. 114-127 ◽  
Author(s):  
Braydon L. Burgess ◽  
Sean A. McIsaac ◽  
Kathryn E. Naus ◽  
Jeniffer Y. Chan ◽  
Gavin H.K. Tansley ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Amyloid Deposition ◽  
Plasma Triglyceride ◽  
Elevated Plasma

scholarly journals Ageing-associated myelin dysfunction drives amyloid deposition in mouse models of Alzheimer's disease

2021 ◽  
Author(s):  
Constanze Depp ◽  
Ting Sun ◽  
Andrew Octavian Sasmita ◽  
Lena Spieth ◽  
Stefan A. Berghoff ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Mouse Models ◽  
Structural Integrity ◽  
Amyloid Β ◽  
Amyloid Deposition ◽  
Structural Defects ◽  
Light Sheet Microscopy ◽  
Brain Ageing

The prevalence of Alzheimer's disease (AD), the leading cause of dementia, shows a strict age-dependency, but why ageing constitutes the main risk factor for this disease is still poorly understood. Brain ageing affects oligodendrocytes and the structural integrity of myelin sheaths, the latter associated with secondary neuroinflammation. Since oligodendrocytes support axonal and neuronal health, we hypothesised that ageing-associated loss of myelin integrity could be an upstream risk factor for neuronal amyloid-β (Aβ) deposition, the primary neuropathological hallmark of AD. Here, we show that in AD mouse models different genetically induced defects of myelin integrity or demyelinating injuries are indeed potent drivers of amyloid deposition in vivo, quantified by whole brain light sheet microscopy. Conversely, the lack of myelin in the forebrain provides protection against plaque deposition. Mechanistically, we find that myelin dysfunction causes the accumulation of the Aβ producing machinery within axonal swellings and increases cortical amyloid precursor protein (APP) cleavage. Surprisingly, AD mice with dysfunctional myelin lack plaque-corralling microglia but show a disease-associated microglia (DAM)-like signature as revealed by bulk and single cell transcriptomics. These activated microglia, however, are primarily engaged with myelin, preventing the protective reactions of microglia to Aβ plaques. Our data suggest a working model, in which age-dependent structural defects of myelin promote plaque formation, directly and indirectly, and are thus an upstream AD risk factor. Improving oligodendrocyte health and myelin integrity could be a promising target to delay AD.

scholarly journals CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models

2010 ◽  
Vol 177 (5) ◽  
pp. 2549-2562 ◽  
Author(s):  
Sungho Lee ◽  
Nicholas H. Varvel ◽  
Megan E. Konerth ◽  
Guixiang Xu ◽  
Astrid E. Cardona ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Microglial Activation ◽  
Beta Amyloid ◽  
Amyloid Deposition

scholarly journals Curcugreen Treatment Prevented Splenomegaly and Other Peripheral Organ Abnormalities in 3xTg and 5xFAD Mouse Models of Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 899
Author(s):  
Jayeeta Manna ◽  
Gary L. Dunbar ◽  
Panchanan Maiti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Amyloid Deposition ◽  
Tunel Staining ◽  
Western Blots ◽  
Peripheral Organ ◽  
Apoptotic Death ◽  
Anti Inflammatory ◽  
5Xfad Mice

Metabolic dysfunction and immune disorders are common in Alzheimer’s disease (AD). The mechanistic details of these epiphenomena in AD are unclear. Here, we have investigated whether a highly bioavailable curcuminoid formulation, curcugreen (CGR), can prevent abnormalities in peripheral organs of two mouse models of AD. Eighteen- and 24-month-old male and female 3xTg and 5xFAD mice were treated with CGR (100 mg/kg) for 2 months, orally. Cytoarchitectural changes of spleen, liver, kidney and lungs were studied by H&E stain. Apoptotic death was confirmed by TUNEL staining. Amyloid deposition, pTau levels, proinflammatory, anti-inflammatory and cell death/survival markers were studied by Western blots. Curcugreen reduced the observed splenomegaly (3xTg) and degeneration of spleen, granulomatous inflammation in the kidney, hepatic sinusoidal disorganization, hepatocellular hypertrophy, inflammation of the central hepatic vein, infiltration and swelling of lung tissues, and apoptotic death in all these areas in both 3xTg and 5xFAD mice. Similarly, CGR decreased amyloid deposition, pTau, proinflammatory markers, cell loss and decrements in anti-inflammatory markers in both 3xTg and 5xFAD mice. Peripheral organ abnormalities and inflammatory responses in AD were ameliorated by curcuminoid treatment.

Biological Signatures of Alzheimer’s Disease

2020 ◽  
Vol 20 (9) ◽  
pp. 770-781 ◽  
Author(s):  
Poornima Sharma ◽  
Anjali Sharma ◽  
Faizana Fayaz ◽  
Sharad Wakode ◽  
Faheem H. Pottoo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Senile Plaque ◽  
Senile Plaques ◽  
Amyloid Deposition ◽  
Immune Defense ◽  
Amyloid Angiopathy ◽  
Microvascular Changes ◽  
Β Amyloid

Alzheimer’s disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition are among the main causes of AD. Amyloid deposition is considered as a central event which induces the link between the production of β amyloid and vascular changes. Presence of numerous biomarkers such as cerebral amyloid angiopathy, microvascular changes, senile plaques, changes in white matter, granulovascular degeneration specifies the manifestation of AD while an aggregation of tau protein is considered as a primary marker of AD. Likewise, microvascular changes, activation of microglia (immune defense system of CNS), amyloid-beta aggregation, senile plaque and many more biomarkers are nearly found in all Alzheimer’s patients. It was seen that 70% of Alzheimer’s cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factors for the later onset of AD. Several pathological changes also occur in the white matter which include dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review, we aim to highlight the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.

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