Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs.

Burdick, Debra; Soreghan, Brian A.; Kwon, Michael; Kosmoski, Joseph V.; Knauer, Mary F.; Henschen, Agnes; Yates, John R.; Cotman, Carl W.; Glabe, Charles G.

doi:10.1016/s0021-9258(18)48529-8

Cited by 911 publications

(296 citation statements)

References 41 publications

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“…In our study, Aβ in neurons aggregated in a concentration-dependent manner. This is consistent with previous studies in SHSY5Y cells and in buffers [ 16 , 19 ]. Besides, the size of Aβ vesicles also showed a significant negative correlation with aggregation in cells with 24 h treatment of higher Aβ concentration, but not in lower concentration.…”

Section: Discussionsupporting

confidence: 94%

“…The concentration of Aβ42 in those vesicles is much higher than in extracellular space [ 16 ]. Low pH in the lysosomes/late endosomes might promote Aβ aggregation [ 19 , 23 ]. Considering the high concentration and low pH, Aβ monomers in these vesicles are more likely to be taken up extracellularly rather than depolymerized from oligomers.…”

Section: Discussionmentioning

confidence: 99%

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Live Cell FRET Imaging Reveals Amyloid β-Peptide Oligomerization in Hippocampal Neurons

Wennmalm

Winblad

Schedin‐Weiss

et al. 2021

IJMS

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Amyloid β-peptide (Aβ) oligomerization is believed to contribute to the neuronal dysfunction in Alzheimer disease (AD). Despite decades of research, many details of Aβ oligomerization in neurons still need to be revealed. Förster resonance energy transfer (FRET) is a simple but effective way to study molecular interactions. Here, we used a confocal microscope with a sensitive Airyscan detector for FRET detection. By live cell FRET imaging, we detected Aβ42 oligomerization in primary neurons. The neurons were incubated with fluorescently labeled Aβ42 in the cell culture medium for 24 h. Aβ42 were internalized and oligomerized in the lysosomes/late endosomes in a concentration-dependent manner. Both the cellular uptake and intracellular oligomerization of Aβ42 were significantly higher than for Aβ40. These findings provide a better understanding of Aβ42 oligomerization in neurons.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Live Cell FRET Imaging Reveals Amyloid β-Peptide Oligomerization in Hippocampal Neurons

Wennmalm

Winblad

Schedin‐Weiss

et al. 2021

IJMS

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show abstract

“…Cerebral pH regulation is crucial for cell functioning, enzyme activity and protein folding and pH status provides information that pertains to cell viability and neuronal degeneration ( Chesler, 2003 ). Previous studies reveal that abnormal cerebral pH has an important role in the aggregation of Alzheimer-associated proteins ( Atwood et al, 1998 ; Barrow and Zagorski, 1991 ; Burdick et al, 1992 ). Some studies also indicate that the reduced intracellular cerebral pH is a consequence of neuroinflammation involved in the development of AD ( Fang et al, 2010 ; Morales et al, 2014 ; Schwartz et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Early detection of Alzheimer's disease using creatine chemical exchange saturation transfer magnetic resonance imaging

Chen¹,

Zijl²,

Wei³

et al. 2021

NeuroImage

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Detecting Alzheimer’s disease (AD) at an early stage brings a lot of benefits including disease management and actions to slow the progression of the disease. Here, we demonstrate that reduced creatine chemical exchange saturation transfer (CrCEST) contrast has the potential to serve as a new biomarker for early detection of AD. The results on wild type (WT) mice and two age-matched AD models, namely tauopathy (Tau) and A β amyloidosis (APP), indicated that CrCEST contrasts of the cortex and corpus callosum in the APP and Tau mice were significantly reduced compared to WT counterpart at an early stage (6-7 months) ( p < 0.011). Two main causes of the reduced CrCEST contrast, i.e. cerebral pH and creatine concentration, were investigated. From phantom and hypercapnia experiments, CrCEST showed excellent sensitivity to pH variations. From MRS results, the creatine concentration in WT and AD mouse brain was equivalent, which suggests that the reduced CrCEST contrast was dominated by cerebral pH change involved in the progression of AD. Immunohistochemical analysis revealed that the abnormal cerebral pH in AD mice may relate to neuroinflammation, a known factor that can cause pH reduction.

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“…1999b), conditions the nature of Aβ released that can be of 40 or 42 amino‐acids long (Checler 1995). This is not anecdotic since the latter species is more prone to aggregation (Burdick et al. 1992), more toxic (El Khoury et al.…”

mentioning

confidence: 99%

The physiology of the β‐amyloid precursor protein intracellular domain AICD

Pardossi‐Piquard

Checler

2011

Journal of Neurochemistry

139

136

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The amyloid-b precursor protein (bAPP) undergoes several cleavages by enzymatic activities called secretases. Numerous studies aimed at studying the biogenesis and catabolic fate of Ab peptides, the proteinaceous component of the senile plaques that accumulate in Alzheimer's disease-affected brains. Relatively recently, another secretase-mediated b-APP-derived catabolite called APP IntraCellular Domain (AICD) entered the game. Whether AICD corresponded to a biologically inert by-pass product of bAPP processing or whether it could harbor its own function remained questionable. In this study, we review the mechanisms by which AICD is generated and how its production is regulated. Furthermore, we discuss the degradation mechanism underlying its rapid catabolic fate. Finally, we review putative AICD-related functions and more particularly, the numerous studies indicating that AICD could translocate to the nucleus and control at a transcriptional level, the expression of a series of proteins involved in various functions including the control of cell death and Ab degradation.

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Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs.

Cited by 911 publications

References 41 publications

Live Cell FRET Imaging Reveals Amyloid β-Peptide Oligomerization in Hippocampal Neurons

Live Cell FRET Imaging Reveals Amyloid β-Peptide Oligomerization in Hippocampal Neurons

Early detection of Alzheimer's disease using creatine chemical exchange saturation transfer magnetic resonance imaging

The physiology of the β‐amyloid precursor protein intracellular domain AICD

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