scholarly journals Maternal antibodies facilitate Amyloid-β clearance by activating Fc-receptor-Syk-mediated phagocytosis

2020 ◽  
Author(s):  
Tomer Illouz ◽  
Raneen Nicola ◽  
Linoy Ben-Shuhan ◽  
Ravit Madar ◽  
Arya Biragyn ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Short Term Memory ◽  
Passive Immunization ◽  
Amyloid Β ◽  
Memory Deficits ◽  
Maternal Antibodies ◽  
Dependent Manner ◽  
Short Term ◽  
Wild Type Female ◽  
Potential Strategy

AbstractDown Syndrome (DS) features a life-long overexpression of the APP and DYRK1A genes, leading to a cognitive decline mediated by Amyloid-β (Aβ) overproduction and tau hyper-phosphorylation. As DS can be diagnosed in utero, maternally transferred anti-Aβ antibodies might promote removal of early accumulation of Aβ from the CNS. A DNA-vaccine expressing Aβ1-11 was delivered to wild-type female mice, followed by mating with 5xFAD males, which exhibit early Aβ plaque formation, similar to individuals with DS. Maternal Aβ-specific antibodies provided transgenic offspring with passive immunization against Aβ via the placental and subsequently lactation. Maternal antibodies reduced cortical Aβ levels 4 months after antibodies were undetectable, along with alleviating short-term memory deficits and activation of the FcγR1/Syk/Cofilin pathway in microglia. Sera from immunized dams facilitated Aβ clearance by microglia in a Syk-dependent manner. These data suggest that maternal anti-Aβ immunization is a potential strategy to alleviate cognitive decline in individuals with DS.

scholarly journals Maternal antibodies facilitate Amyloid-β clearance by activating Fc-receptor-Syk-mediated phagocytosis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Tomer Illouz ◽  
Raneen Nicola ◽  
Linoy Ben-Shushan ◽  
Ravit Madar ◽  
Arya Biragyn ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Protein Misfolding ◽  
Short Term Memory ◽  
Amyloid Β ◽  
Maternal Antibodies ◽  
Microglial Phenotype ◽  
Endogenous Protein ◽  
Wild Type Female ◽  
The Central Nervous System ◽  
Protein Misfolding And Aggregation

AbstractMaternal antibodies (MAbs) protect against infections in immunologically-immature neonates. Maternally transferred immunity may also be harnessed to target diseases associated with endogenous protein misfolding and aggregation, such as Alzheimer’s disease (AD) and AD-pathology in Down syndrome (DS). While familial early-onset AD (fEOAD) is associated with autosomal dominant mutations in the APP, PSEN1,2 genes, promoting cerebral Amyloid-β (Aβ) deposition, DS features a life-long overexpression of the APP and DYRK1A genes, leading to a cognitive decline mediated by Aβ overproduction and tau hyperphosphorylation. Although no prenatal screening for fEOAD-related mutations is in clinical practice, DS can be diagnosed in utero. We hypothesized that anti-Aβ MAbs might promote the removal of early Aβ accumulation in the central nervous system of human APP-expressing mice. To this end, a DNA-vaccine expressing Aβ1-11 was delivered to wild-type female mice, followed by mating with 5xFAD males, which exhibit early Aβ plaque formation. MAbs reduce the offspring’s cortical Aβ levels 4 months after antibodies were undetectable, along with alleviating short-term memory deficits. MAbs elicit a long-term shift in microglial phenotype in a mechanism involving activation of the FcγR1/Syk/Cofilin pathway. These data suggest that maternal immunization can alleviate cognitive decline mediated by early Aβ deposition, as occurs in EOAD and DS.

scholarly journals Optimizing Subjective Cognitive Decline to Detect Early Cognitive Dysfunction

2021 ◽  
Vol 80 (3) ◽  
pp. 1185-1196
Author(s):  
Silvia Chapman ◽  
Preeti Sunderaraman ◽  
Jillian L. Joyce ◽  
Martina Azar ◽  
Leigh E. Colvin ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cognitive Dysfunction ◽  
Associative Memory ◽  
Short Term Memory ◽  
Subjective Cognitive Decline ◽  
Short Term ◽  
Term Memory ◽  
Memory Binding ◽  
Preclinical Ad ◽  
List Learning

Background: The utility of subjective cognitive decline (SCD) as an indicator of preclinical AD is overshadowed by its inconsistent association with objective cognition. Objective: This study examines if manipulations of SCD measurement affect its association with early cognitive dysfunction characteristic of preclinical AD. Methods: Cognitively healthy older adults (n = 110) completed SCD questionnaires that elicited complaints in general, compared to 5 years ago (retrospective SCD) and compared to their peers (age-anchored SCD) in binary and Likert scales. Outcome cognitive tasks included an associative memory task (Face-Name Test), a visual short-term memory binding task (STMB test), and a clinical neuropsychological list learning test (Selective Reminder Test). Results: SCD complaints, when compared to age-matched peers (age-anchored SCD) were endorsed less frequently than complaints compared to 5 years ago (retrospective SCD) (p < 0.01). In demographically adjusted regressions, age-anchored ordinal-rated SCD was associated with short term memory binding (β= –0.22, p = 0.040, CI = –0.45, –0.01), associative memory (β= –0.26, p = 0.018, CI = –0.45, –0.06), and list learning (β= –0.31, p = 0.002, CI = –0.51, –0.12). Retrospective and general ordinal-rated SCD was associated with associative memory (β= –0.25, p = 0.012, CI = –0.44, –0.06; β= –0.29, p = 0.003, CI = –0.47, –0.10) and list learning only (β= –0.25, p = 0.014, CI = –0.45, –0.05; β= –0.28, p = 0.004, CI = –0.48, –0.09). Conclusion: Ordinal age-anchored SCD appears better suited than other SCD measurements to detect early cognitive dysfunction characteristic of preclinical AD.

scholarly journals Explaining semantic short-term memory deficits: Evidence for the critical role of semantic control

2011 ◽  
Vol 49 (3) ◽  
pp. 368-381 ◽  
Author(s):  
Paul Hoffman ◽  
Elizabeth Jefferies ◽  
Matthew A. Lambon Ralph
Keyword(s):  
Short Term Memory ◽  
Critical Role ◽  
Memory Deficits ◽  
Short Term ◽  
Term Memory

scholarly journals Electroconvulsive therapy hasn’t negative effects on short-term memory function, as assessed using a bedside hand-held device

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Helge H.O. Müller ◽  
Mareen Reike ◽  
Simon Grosse-Holz ◽  
Mareike Röther ◽  
Caroline Lücke ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Electroconvulsive Therapy ◽  
Short Term Memory ◽  
Memory Function ◽  
Memory Deficits ◽  
Treatment Resistant ◽  
Negative Effects ◽  
Short Term ◽  
Term Memory ◽  
Digital Measurements

Electroconvulsive therapy (ECT) is effective in the treatment of treatment-resistant major depression. The fear of cognitive impairment after ECT often deters patients from choosing this treatment option. There is little reliable information regarding the effects of ECT on overall cognitive performance, while short-term memory deficits are well known but not easy to measure within clinical routines. In this pilot study, we examined ECT recipients’ pre- and posttreatment performances on a digital ascending number tapping test. We found that cognitive performance measures exhibited good reproducibility in individual patients and that ECT did not significantly alter cognitive performance up to 2 hours after this therapy was applied. Our results can help patients and physicians make decisions regarding the administration of ECT. Digital measurements are recommended, especially when screening for the most common side effects on cognitive performance and short-term memory.

scholarly journals Selective memory and behavioral alterations after ambient ultrafine particulate matter exposure in aged 3xTgAD Alzheimer’s disease mice

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Katrina Jew ◽  
Denise Herr ◽  
Candace Wong ◽  
Andrea Kennell ◽  
Keith Morris-Schaffer ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Short Term Memory ◽  
Memory Deficits ◽  
Olfactory Discrimination ◽  
Spatial Learning And Memory ◽  
Short Term ◽  
Term Memory ◽  
Appetitive Motivation

Abstract Background A growing body of epidemiological literature indicates that particulate matter (PM) air pollution exposure is associated with elevated Alzheimer’s disease (AD) risk and may exacerbate AD-related cognitive decline. Of concern is exposure to the ultrafine PM (UFP) fraction (≤100 nm), which deposits efficiently throughout the respiratory tract, has higher rates of translocation to secondary organs, like brain, and may induce inflammatory changes. We, therefore, hypothesize that exposure to UFPs will exacerbate cognitive deficits in a mouse model of AD. The present study assessed alterations in learning and memory behaviors in aged (12.5 months) male 3xTgAD and non-transgenic mice following a 2-week exposure (4-h/day, 4 days/week) to concentrated ambient UFPs using the Harvard ultrafine concentrated ambient particle system (HUCAPS) or filtered air. Beginning one month following exposure, locomotor activity, spatial learning and memory, short-term recognition memory, appetitive motivation, and olfactory discrimination were assessed. Results No effects on locomotor activity were found following HUCAPS exposure (number concentration, 1 × 104–4.7 × 105 particles/cm3; mass concentration, 29–132 μg/m3). HUCAPS-exposed mice, independent of AD background, showed a significantly decreased spatial learning, mediated through reference memory deficits, as well as short-term memory deficits in novel object recognition testing. AD mice displayed diminished spatial working memory, potentially a result of olfactory deficits, and short-term memory. AD background modulated HUCAPS-induced changes on appetitive motivation and olfactory discrimination, specifically enhancing olfactory discrimination in NTg mice. Modeling variation in appetitive motivation as a covariate in spatial learning and memory, however, did not support the conclusion that differences in motivation significantly underlie changes in spatial learning and memory. Conclusions A short-term inhalation exposure of aged mice to ambient UFPs at human-relevant concentrations resulted in protracted (testing spanning 1–6.5 months post-exposure) adverse effects on multiple memory domains (reference and short-term memory) independent of AD background. Impairments in learning and memory were present when accounting for potential covariates like motivational changes and locomotor activity. These results highlight the need for further research into the potential mechanisms underlying the cognitive effects of UFP exposure in adulthood.

Nobiletin, a flavone from Citrus depressa, induces gene expression and increases the protein level and activity of neprilysin in SK-N-SH cells

2014 ◽  
Vol 92 (5) ◽  
pp. 351-355 ◽  
Author(s):  
Hironori Fujiwara ◽  
Junko Kimura ◽  
Masahiro Sakamoto ◽  
Akihito Yokosuka ◽  
Yoshihiro Mimaki ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Time Dependent ◽  
Amyloid Β Protein ◽  
Dependent Manner ◽  
Disease Modifying Drugs ◽  
Β Protein ◽  
Gene And Protein Expression ◽  
Polymerase Chain ◽  
Potential Strategy ◽  
The Brain

Neprilysin (NEP) is one of the candidate amyloid β protein (Aβ) degrading enzymes affecting brain Aβ clearance. This enzyme declines in the brain with age, which leads to the increased Aβ deposition in Alzheimer’s disease (AD). Pharmacological activation of NEP during the aging process, therefore, represents a potential strategy to prevent the development of AD. To examine the influence of nobiletin on neprilysin activity, we measured cellular NEP activity in SK-N-SH cells. Moreover, NEP expression was examined by using reverse transcription – polymerase chain reaction and Western blotting. Measurement of cellular NEP activity showed that nobiletin stimulated this in a dose- and time-dependent manner in SK-N-SH cells. Moreover, nobiletin increased the expression of NEP mRNA, and then the levels of NEP protein, also in a dose- and time-dependent manner. Our findings showed that nobiletin promoted NEP gene and protein expression, resulting in enhancement of cellular NEP activity in SK-N-SH cells. This compound could be a novel Aβ-degrading compound for use in the development of disease-modifying drugs to prevent and (or) cure AD.

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