Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.

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The Neuronal Actions of Leptin and the Implications for Treating Alzheimer’s Disease

Pharmaceuticals ◽

10.3390/ph14010052 ◽

2021 ◽

Vol 14 (1) ◽

pp. 52

Author(s):

Kirsty Hamilton ◽

Jenni Harvey

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Energy Homeostasis ◽

Leptin Receptor ◽

Hippocampal Formation ◽

Synaptic Function ◽

Receptor Expression ◽

Neuroprotective Actions ◽

Novel Target ◽

Leptin System

It is widely accepted that the endocrine hormone leptin controls food intake and energy homeostasis via activation of leptin receptors expressed on hypothalamic arcuate neurons. The hippocampal formation also displays raised levels of leptin receptor expression and accumulating evidence indicates that leptin has a significant impact on hippocampal synaptic function. Thus, cellular and behavioural studies support a cognitive enhancing role for leptin as excitatory synaptic transmission, synaptic plasticity and glutamate receptor trafficking at hippocampal Schaffer collateral (SC)-CA1 synapses are regulated by leptin, and treatment with leptin enhances performance in hippocampus-dependent memory tasks. Recent studies indicate that hippocampal temporoammonic (TA)-CA1 synapses are also a key target for leptin. The ability of leptin to regulate TA-CA1 synapses has important functional consequences as TA-CA1 synapses are implicated in spatial and episodic memory processes. Moreover, degeneration is initiated in the TA pathway at very early stages of Alzheimer’s disease, and recent clinical evidence has revealed links between plasma leptin levels and the incidence of Alzheimer’s disease (AD). Additionally, accumulating evidence indicates that leptin has neuroprotective actions in various AD models, whereas dysfunctions in the leptin system accelerate AD pathogenesis. Here, we review the data implicating the leptin system as a potential novel target for AD, and the evidence that boosting the hippocampal actions of leptin may be beneficial.

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Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer’s disease

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1611073113 ◽

2016 ◽

Vol 113 (42) ◽

pp. E6535-E6544 ◽

Cited By ~ 68

Author(s):

Xiuming Zhang ◽

Elizabeth C. Mormino ◽

Nanbo Sun ◽

Reisa A. Sperling ◽

Mert R. Sabuncu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Executive Function ◽

Bayesian Model ◽

Late Onset ◽

Temporal Cortex ◽

Cortical Atrophy ◽

Future Research ◽

Dementia Patients ◽

With Memory

We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer’s disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid–positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research.

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Plasma cortisol and norepinephrine in Alzheimer’s disease: opposite relations with recall performance and stage of progression

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2006.00172.x ◽

2007 ◽

Vol 19 (4) ◽

pp. 231-237 ◽

Cited By ~ 2

Author(s):

Karel J. Bemelmans ◽

Annemarie Noort ◽

Roel de Rijk ◽

Huub A. M. Middelkoop ◽

Godfried M. J. van Kempen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hippocampal Neurons ◽

Plasma Cortisol ◽

Recall Performance ◽

Area Under The Curve ◽

Plasma Norepinephrine ◽

Clinical Dementia Rating ◽

Memory Decline ◽

Word Lists

Objective:Alzheimer’s disease (AD) is characterized by effortful retrieval memory impairments, loss of hippocampal neurons and elevated plasma cortisol (CORT) concentrations. The latter could induce further memory decline. AD is also characterized by increased central and peripheral noradrenergic activity. Since noradrenergic function is involved in memory formation, this upregulated function could counteract memory decline. The aim of the present study was to test these hypotheses using plasma norepinephrine (NE) as a noradrenergic parameter, and recall of the prerecency part of neutral valence word lists as a measure of effortful retrieval.Methods:Area under the curve (AUC) of morning, midday and afternoon plasma CORT and plasma NE concentrations was related to two measures of recall performance, ie summated recall scores of the prerecency and recency parts of three word lists, and to the stage of the Clinical Dementia Rating (CDR).Results:Partial correlation between each hormone AUC value and prerecency recall performance, controlling for the effect of the other hormone, showed opposite relations between recall and either plasma CORT or NE. Similar stronger correlations were found with the CDR score.Conclusions:Plasma CORT and NE are oppositely related with effortful retrieval and the stage of progression in AD.

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Rosiglitazone reverses memory decline and hippocampal glucocorticoid receptor down-regulation in an Alzheimer’s disease mouse model

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2008.12.071 ◽

2009 ◽

Vol 379 (2) ◽

pp. 406-410 ◽

Cited By ~ 89

Author(s):

Luis Escribano ◽

Ana-María Simón ◽

Alberto Pérez-Mediavilla ◽

Pablo Salazar-Colocho ◽

Joaquín Del Río ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Glucocorticoid Receptor ◽

Down Regulation ◽

Memory Decline

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Therapeutic potential of astaxanthin and superoxide dismutase in Alzheimer's disease

Open Biology ◽

10.1098/rsob.210013 ◽

2021 ◽

Vol 11 (6) ◽

pp. 210013

Author(s):

Vyshnavy Balendra ◽

Sandeep Kumar Singh

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Superoxide Dismutase ◽

Antioxidant System ◽

Tau Protein ◽

Therapeutic Potential ◽

Plaque Burden ◽

Memory Decline ◽

Endogenous Antioxidants ◽

The Brain

Oxidative stress, the imbalance of the antioxidant system, results in an accumulation of neurotoxic proteins in Alzheimer's disease (AD). The antioxidant system is composed of exogenous and endogenous antioxidants to maintain homeostasis. Superoxide dismutase (SOD) is an endogenous enzymatic antioxidant that converts superoxide ions to hydrogen peroxide in cells. SOD supplementation in mice prevented cognitive decline in stress-induced cells by reducing lipid peroxidation and maintaining neurogenesis in the hippocampus. Furthermore, SOD decreased expression of BACE1 while reducing plaque burden in the brain. Additionally, Astaxanthin (AST), a potent exogenous carotenoid, scavenges superoxide anion radicals. Mice treated with AST showed slower memory decline and decreased depositions of amyloid-beta (A β ) and tau protein. Currently, the neuroprotective potential of these supplements has only been examined separately in studies. However, a single antioxidant cannot sufficiently resist oxidative damage to the brain, therefore, a combinatory approach is proposed as a relevant therapy for ameliorating pathological changes in AD.

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Effect of Letrozole on hippocampal let-7 microRNAs and their correlation with working memory and phosphorylated Tau protein level in an Alzheimer's disease rat model

10.21203/rs.3.rs-444685/v1 ◽

2021 ◽

Author(s):

Nada Alaa Moustafa ◽

Mohammed Abdelhamed El-Sayed ◽

Somia Hassan Abdallah ◽

Noha M. Hazem ◽

Doaa Attia Abdelmoety

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Working Memory ◽

Tau Protein ◽

Sprague Dawley ◽

Qrt Pcr ◽

Sprague Dawley Rats ◽

Conflicting Evidence ◽

With Memory ◽

Phosphorylated Tau Protein

Abstract Let-7 microRNAs may contribute to neurodegeneration, including Alzheimer's disease (AD), but, they were not investigated in Streptozotocin (STZ)-induced AD. Letrozole increases the expression of Let-7 in cell lines, with conflicting evidence regarding its effects on memory. This study examined Let-7 microRNAs in STZ-induced AD, their correlation with memory and hyperphosphorylated Tau (p-Tau) and the effects of Letrozole on them. Seven groups of adult Sprague Dawley rats were used: Intact, Letrozole, Letrozole Vehicle, STZ (with AD induced by intracerebroventricular injection of STZ in artificial CSF), CSF Control, STZ + Letrozole (STZ-L), and CSF + Letrozole Vehicle. Alternation percentage in T-maze was used as a measure of working memory. Let-7a, b and e and p-Tau levels in the hippocampus were estimated using qRT-PCR and ELISA, respectively. There were significant decreases in alternation percentage and increase in p-Tau in the STZ, Letrozole and STZ-L groups. Expression levels of all studied microRNAs were significantly elevated in the Letrozole and the STZ + L groups, with no difference between the two, suggesting that this elevation was due to Letrozole. Negative correlations were found between alternation percentage and the levels of all studied microRNAs, while positive ones were found between p-Tau concentration and the levels of studied microRNAs. These findings support the theory that Letrozole aggravates pre-existing lesions and add to the evidence of Let-7 neurotoxicity.

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ODor-evoked Autobiographical Memory in Alzheimer’s disease?

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acab074 ◽

2021 ◽

Author(s):

Mohamad El Haj

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Autobiographical Memory ◽

Personal Information ◽

Disease Model ◽

Olfactory Stimulation ◽

Autobiographical Memories ◽

Comprehensive Overview ◽

Memory Decline ◽

Stimulation Of

Abstract Objective Because memory decline is the hallmark of Alzheimer’s disease (AD), an important endeavor for both clinicians and researchers is to improve memory performances in AD. This can be pursued by olfactory stimulation of memory in patients with AD and by studying the effects of olfactory stimulation on autobiographical memory (i.e., memory for personal information). The effects of olfactory stimulation on autobiographical memory in patients with mild AD have been reported by recent research. We thus provide the first comprehensive overview of research on odor-evoked autobiographical memory in AD. We also establish the basis for solid theoretical analysis concerning the memory improvement reported by research on odor-evoked autobiographical memory in AD. Method We examined literature on odor-evoked autobiographical memories in AD and propose the “OdAMA” (Odor-evoked Autobiographical Memory in Alzheimer’s disease) model. Results and discussion According to OdAMA model, odor exposure activates involuntary access to specific autobiographical memories, which promotes enhanced experience subjective of retrieval in patients with AD and improves their ability to construct not only recent and remote events but also future ones. The OdAMA model could serve as a guide for researchers and clinicians interested in odor-evoked autobiographical memory in AD.

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