Plasma membrane fragility in dystrophic neurites in senile plaques of Alzheimer's disease: an index of oxidative stress

As life expectancy is growing, neurodegenerative disorders, such as Alzheimer’s disease, are increasing. This disease is characterised by the accumulation of intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein, senile plaques composed of an extracellular deposit of β-amyloid peptide (Aβ), and neuronal loss. This is accompanied by deficient mitochondrial function, increased oxidative stress, altered inflammatory response, and autophagy process impairment. The present study gathers scientific evidence that demonstrates that specific nutrients exert a direct effect on both Aβ production and Tau processing and their elimination by autophagy activation. Likewise, certain nutrients can modulate the inflammatory response and the oxidative stress related to the disease. However, the extent to which these effects come with beneficial clinical outcomes remains unclear. Even so, several studies have shown the benefits of the Mediterranean diet on Alzheimer’s disease, due to its richness in many of these compounds, to which can be attributed their neuroprotective properties due to the pleiotropic effect they show on the aforementioned processes. These indications highlight the potential role of adequate dietary recommendations for clinical management of both Alzheimer’s diagnosed patients and those in risk of developing it, emphasising once again the importance of diet on health.

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Selective PrP-like protein, doppel immunoreactivity in dystrophic neurites of senile plaques in Alzheimer's disease

Neuropathology and Applied Neurobiology ◽

10.1111/j.1365-2990.2003.00534.x ◽

2004 ◽

Vol 30 (4) ◽

pp. 329-337 ◽

Cited By ~ 10

Author(s):

I. Ferrer ◽

M. Freixas ◽

R. Blanco ◽

M. Carmona ◽

B. Puig

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Senile Plaques ◽

Dystrophic Neurites

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The Triggering Receptor Expressed on Myeloid Cells 2: “TREM-ming” the Inflammatory Component Associated with Alzheimer's Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/860959 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 19

Author(s):

Troy T. Rohn

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurofibrillary Tangles ◽

Neurodegenerative Disorder ◽

Late Onset ◽

Senile Plaques ◽

Myeloid Cells ◽

Disease Process ◽

Age Related

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by a progressive loss of memory and cognitive skills. Although much attention has been devoted concerning the contribution of the microscopic lesions, senile plaques, and neurofibrillary tangles to the disease process, inflammation has long been suspected to play a major role in the etiology of AD. Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a major contributing factor in AD. Variants in TREM2 triple one's risk of developing late-onset AD. TREM2 is expressed on microglial cells, the resident macrophages in the CNS, and functions to stimulate phagocytosis on one hand and to suppress cytokine production and inflammation on the other hand. The purpose of this paper is to discuss these recent developments including the potential role that TREM2 normally plays and how loss of function may contribute to AD pathogenesis by enhancing oxidative stress and inflammation within the CNS. In this context, an overview of the pathways linking beta-amyloid, neurofibrillary tangles (NFTs), oxidative stress, and inflammation will be discussed.

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Immune System Response in Alzheimer's Disease

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100029863 ◽

1989 ◽

Vol 16 (S4) ◽

pp. 516-527 ◽

Cited By ~ 323

Author(s):

P.L. McGeer ◽

H. Akiyama ◽

S. Itagaki ◽

E.G. McGeer

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immune System ◽

Brain Tissue ◽

Senile Plaques ◽

Class Ii ◽

Dystrophic Neurites ◽

Reactive Microglia ◽

Alzheimer Brain ◽

Alternative Complement

ABSTRACT:Involvement of the immune system in the pathogenesis of Alzheimer's disease was demonstrated in two ways: by the attachment of complement proteins to diseased tissue, and by the activation of cells associated with the immune system. Alzheimer brain tissue was stained immunohistochemically by antibodies to components of the classical, but not the alternative, complement pathway. Antibodies to Clq, C3d, and C4d stained senile plaques, dystrophic neurites, neuropil threads and some tangled neurons. Antibodies to a neoantigenic site on the C5b-9 membrane attack complex stained dystrophic neurites and many tangled neurons, but not senile plaques. Antibodies to Factor P and fraction Bb of Factor B, which are specific for the alternative complement pathway, did not stain Alzheimer brain tissue. The cellular immune response was evaluated by the presence of reactive microglia and by the infiltration of small numbers of T-cells into diseased brain tissue. Reactive microglia were identified by antibodies to HLA-DR, a class II major histocompatibility complex glycoprotein, and by enhanced staining with antibodies to leukocyte common antigen and the FC7RI and FcyRII receptors. T-cells were identified by antibodies to leukocyte common antigen, as well as the CD4 and CD8 surface proteins. Double immunostaining with antibodies to GFAP and MHC class I or class II antigens established that astrocytes, which are GFAP positive, do not express MHC antigens in Alzheimer's disease. Endothelial cells express MHC class I antigens while reactive microglia and some leukocytes express class II antigen.

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Impairment of the activity of the plasma membrane Ca2+-ATPase in Alzheimer's disease

Biochemical Society Transactions ◽

10.1042/bst0390819 ◽

2011 ◽

Vol 39 (3) ◽

pp. 819-822 ◽

Cited By ~ 18

Author(s):

Ana M. Mata ◽

María Berrocal ◽

M. Rosario Sepúlveda

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Plasma Membrane ◽

Molecular Mechanisms ◽

Neurodegenerative Disorder ◽

Senile Plaques ◽

Amyloid Β ◽

Inhibitory Effect ◽

Amyloid Β Peptide ◽

Aβ Amyloid

AD (Alzheimer's disease) is an age-associated neurodegenerative disorder where the accumulation of neurotoxic Aβ (amyloid β-peptide) in senile plaques is a typical feature. Recent studies point out a relationship between Aβ neurotoxicity and Ca2+ dyshomoeostasis, but the molecular mechanisms involved are still under discussion. The PMCAs (plasma membrane Ca2+-ATPases) are a multi-isoform family of proteins highly expressed in brain that is implicated in the maintenance of low intraneural Ca2+ concentration. Therefore the malfunction of this pump may also be responsible for Ca2+ homoeostasis failure in AD. We have found that the Ca2+-dependence of PMCA activity is affected in human brains diagnosed with AD, being related to the enrichment of Aβ. The peptide produces an inhibitory effect on the activity of PMCA which is isoform-specific, with the greatest inhibition of PMCA4. Besides, cholesterol blocked the inhibitory effect of Aβ, which is consistent with the lack of any Aβ effect on PMCA4 found in cholesterol-enriched lipid rafts isolated from pig brain. These observations suggest that PMCAs are a functional component of the machinery that leads to Ca2+ dysregulation in AD and propose cholesterol enrichment in rafts as a protector of the Aβ-mediated inhibition on PMCA.

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Ubiquitin immunoelectron microscopy of dystrophic neurites in cerebellar senile plaques of Alzheimer's disease

Acta Neuropathologica ◽

10.1007/bf00296107 ◽

1990 ◽

Vol 79 (5) ◽

pp. 486-493 ◽

Cited By ~ 55

Author(s):

D. W. Dickson ◽

A. Wertkin ◽

L. A. Mattiace ◽

E. Fier ◽

Y. Kress ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immunoelectron Microscopy ◽

Senile Plaques ◽

Dystrophic Neurites

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Evidence that transmitter-containing dystrophic neurites precede those containing paired helical filaments within senile plaques in the entorhinal cortex of nondemented elderly and Alzheimer's disease patients

Brain Research ◽

10.1016/0006-8993(93)91595-j ◽

1993 ◽

Vol 619 (1-2) ◽

pp. 55-68 ◽

Cited By ~ 19

Author(s):

William C. Benzing ◽

Daniel R. Brady ◽

Elliott J. Mufson ◽

David M. Armstrong

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Entorhinal Cortex ◽

Senile Plaques ◽

Paired Helical Filaments ◽

Dystrophic Neurites

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Diabetes and Alzheimer’s Disease: Might Mitochondrial Dysfunction Help Deciphering the Common Path?

Antioxidants ◽

10.3390/antiox10081257 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1257

Author(s):

Maria Assunta Potenza ◽

Luca Sgarra ◽

Vanessa Desantis ◽

Carmela Nacci ◽

Monica Montagnani

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Insulin Signaling ◽

Molecular Mechanisms ◽

Senile Plaques ◽

Mitochondrial Activity ◽

Enhanced Production ◽

The Common ◽

The Brain

A growing number of clinical and epidemiological studies support the hypothesis of a tight correlation between type 2 diabetes mellitus (T2DM) and the development risk of Alzheimer’s disease (AD). Indeed, the proposed definition of Alzheimer’s disease as type 3 diabetes (T3D) underlines the key role played by deranged insulin signaling to accumulation of aggregated amyloid beta (Aβ) peptides in the senile plaques of the brain. Metabolic disturbances such as hyperglycemia, peripheral hyperinsulinemia, dysregulated lipid metabolism, and chronic inflammation associated with T2DM are responsible for an inefficient transport of insulin to the brain, producing a neuronal insulin resistance that triggers an enhanced production and deposition of Aβ and concomitantly contributes to impairment in the micro-tubule-associated protein Tau, leading to neural degeneration and cognitive decline. Furthermore, the reduced antioxidant capacity observed in T2DM patients, together with the impairment of cerebral glucose metabolism and the decreased performance of mitochondrial activity, suggests the existence of a relationship between oxidative damage, mitochondrial impairment, and cognitive dysfunction that could further reinforce the common pathophysiology of T2DM and AD. In this review, we discuss the molecular mechanisms by which insulin-signaling dysregulation in T2DM can contribute to the pathogenesis and progression of AD, deepening the analysis of complex mechanisms involved in reactive oxygen species (ROS) production under oxidative stress and their possible influence in AD and T2DM. In addition, the role of current therapies as tools for prevention or treatment of damage induced by oxidative stress in T2DM and AD will be debated.

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The impact of melatonin on antioxidant defense mechanisms in Alzheimer’s disease

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0012.8252 ◽

2018 ◽

Vol 72 ◽

pp. 1114-1122

Author(s):

Daria Malicka ◽

Dominika Markowska ◽

Jarosław Nuszkiewicz ◽

Karolina Szewczyk-Golec

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Defense Mechanisms ◽

Senile Plaques ◽

Biological Clock ◽

Cell Functions ◽

Increased Risk ◽

The Impact ◽

Phosphorylated Tau Protein

During aging, the increased risk of neurodegenerative disease development is observed. One of the most common and most serious disorders is Alzheimer’s disease manifested by the loss of nerve cell functions. In the course of the disease, extracellular senile plaques consisting of beta-amyloid and intracellular neurofibrillary tangles of hyper-phosphorylated tau protein are formed. As a result of aging, the repair potential of damaged nerve cells is reduced. Free radicals formed in excess generate augmented oxidative stress, which contributes to the damaging of biomolecules and the development of pathological changes. This mechanism is favored by a decrease in the efficiency of antioxidant enzymes and the deficiency of antioxidants, observed in aging organism. With age, the secretion of the pineal hormone melatonin, functioning as a biochemical biological clock, is significantly reduced. This compound has been proved to be a very effective antioxidant that plays a key role in protecting cells against excessive damage, especially in nervous tissue. Studies have shown that supplementation with exogenous melatonin can prevent oxidative stress-induced degeneration of neurons. Considering the action of melatonin and the pathogenesis of Alzheimer’s disease, the idea of using the hormone supplementation in the prevention and alleviation of the effects of the disease seems to be extremely interesting.

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