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Low‐density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta‐amyloid Clearance?
Open accessAbstract
In 1985, the Nobel Prize in Physiology or Medicine was awarded jointly to Michael S. Brown and Joseph L. Goldstein for their discoveries on regulation of cholesterol metabolism. Among their findings, they determined that familial hypercholesterolemia (FH) is caused by genetic defects in the low-density lipoprotein receptor (LDLR). FH heterozygotes (1:500) exhibit a 50% deficiency in LDLR expression, which leads to a twofold increase in the number of LDL particles in the blood from birth and an increased risk of cardiovascular disease. This prevalence is sufficiently high to warrant the diagnosis and treatment of FH at primary health care by the World Health Organization. Given its pivotal role in the metabolism of apolipoprotein B-100-containing LDL particles, a great deal of attention has been devoted to understanding the role of the LDLR in the pathogenesis of atherosclerosis and coronary heart disease. In contrast, the physiological and pathological roles of LDLR in the brain are only beginning to be revealed. In this regard, Daniel Zambón and colleagues 1 recently reported that middle-aged patients with FH exhibit a particularly high incidence of mild cognitive impairment (MCI), a transitional state between the cognitive decline observed in the elderly and proper dementia. Of note, Ramirez and colleagues 2 and we 3 corroborated this observation in ApoB100/LDLr−/− and LDLr−/− experimental mouse models of FH, respectively. Specifically, we found that middle-aged LDLr−/− mice exhibited working, spatial reference, and procedural memory impairments without alterations in exploratory activities and anxiety-related responses. Moreover, we did not observe signs of stroke-related features in middle-aged LDLr−/− mice 3. This latter observation agrees with previous clinical data reported by Zambón and colleagues 1 regarding the observation of MCI without cerebrovascular disease in FH patients. Currently, significant research efforts are attempting to investigate the role of LDLR in the development of Alzheimer's disease (AD)-like pathology. Notably, a series of elegant studies have shown that LDLR plays an important role in pathways that modulate amyloid-β (Aβ) metabolism. On one hand, Katsouri and Georgopoulos 4 reported that a lack of LDLR aggravated amyloid deposition in a transgenic mouse model of AD. Conversely, Kim and colleagues 5 demonstrated a marked reduction of amyloid plaque formation in the brains of amyloid precursor protein (APP) transgenic mice that overexpress LDLR. Accordingly, Basak and colleagues 6 demonstrated that modulation of the LDLR levels altered both Aβ uptake and degradation by astrocytes. Deletion of LDLR caused a decrease in Aβ uptake, whereas increased LDLR expression significantly enhanced both Aβ uptake and clearance 6. Taken together, all of these findings clearly indicate that LDLR can regulate Aβ levels. Nonetheless, it is important to note that in a study by Fryer and colleagues 7, LDLR deletion had no effect on amyloid deposition in huAPP transgenic mice. To date, the mechanism by which LDLR modulates Aβ metabolism has remained unclear. It is known that the ε4 allele of the apolipoprotein E (APOE) gene accelerates cerebral amyloid deposition as well as progression from MCI to dementia. Conversely, ApoE deletion in most mouse models of AD was found to significantly inhibit amyloid plaque formation. Although LDLR was shown to regulate ApoE levels in the brain, suggesting that ApoE is a potential key mediator of the LDLR effects on amyloid deposition, Katsouri and Georgopoulos 4 generated 5XFAD/ApoE−/−LDLr−/− mice and compared amyloid deposition in these mice to that in 5XFAD/ApoE−/− mice. Notably, these researchers found that LDLR might be involved in a mechanism affecting amyloid deposition, whereas ApoE was not involved. Moreover, Basak and colleagues 6 found that LDLR is capable of promoting the uptake of Aβ into primary astrocytes even in ApoE−/− cells. Katsouri and Georgopoulos 4 also found that LDLR deletion had no impact on APP processing and production of α and β carboxy terminal fragments in the mouse brain. In their study, Basak and colleagues 6 provided evidence that Aβ can directly bind to LDLR, suggesting that an interaction between LDLR and Aβ could be responsible for LDLR-mediated Aβ uptake. Specifically, the authors showed via immunoprecipitation and surface plasmon resonance that both Aβ40 and Aβ42 could bind to the extracellular domain of LDLR with KD values of 47.4 and 37.4 nm, respectively 6. Kim and colleagues 5 demonstrated that LDLR overexpression decreases amyloid deposition by altering the steady-state concentration of Aβ in the brain interstitial fluid (ISF). Notably, Castellano and colleagues 8 used a brain efflux index method to demonstrate a unique role for LDLR in the blood–brain barrier (BBB)-mediated Aβ clearance. Specifically, these authors found that LDLR overexpression significantly increased the appearance rate of endogenously produced human
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AI snapshot
Written from the paper’s full text.
TL;DR
This short review argues that the low-density lipoprotein receptor (LDLR) regulates cerebral amyloid-β (Aβ) metabolism and clearance, making it a candidate therapeutic target for Alzheimer's disease. It synthesizes mouse and clinical evidence linking LDLR loss to cognitive impairment and increased amyloid burden, while noting that the underlying mechanism remains unresolved.
Key findings
- Middle-aged patients with familial hypercholesterolemia (FH) show a particularly high incidence of mild cognitive impairment (MCI), corroborated in ApoB100/LDLr−/− and LDLr−/− mouse models; middle-aged LDLr−/− mice showed working, spatial reference, and procedural memory impairments without altered exploratory/anxiety responses or signs of stroke-related features.
- LDLR loss aggravated amyloid deposition in a transgenic AD mouse model, whereas LDLR overexpression markedly reduced amyloid plaque formation and altered steady-state Aβ in brain interstitial fluid; LDLR modulation altered astrocytic Aβ uptake and degradation (deletion decreased uptake, increased expression enhanced uptake and clearance).
- Aβ40 and Aβ42 bind the LDLR extracellular domain with K_D values of 47.4 and 37.4 nM, respectively, suggesting direct LDLR–Aβ interaction mediates uptake; LDLR overexpression also increased the appearance rate of brain-derived human Aβ in blood via BBB-mediated clearance.
- Absence of LDLR potentiated Aβ-induced neurotoxicity: LDLr−/− mice given acute intracerebroventricular Aβ1-40 showed increased astrogliosis, oxidative stress, and cell permeability in the hippocampus versus identically treated wild-type C57Bl/6 mice.
Methods
- Narrative review/commentary synthesizing prior clinical and experimental literature; no new primary data are reported.
- Evidence discussed includes FH patient cohorts, LDLr−/− and ApoB100/LDLr−/− mouse models, APP/5XFAD transgenic AD models, immunoprecipitation and surface plasmon resonance binding assays, brain efflux index measurements, and intracerebroventricular Aβ1-40 injection experiments.
- The authors propose that compounds increasing hepatic LDLR (tamoxifen, statins, gemfibrozil) and strategies raising glial LDLR warrant investigation in amyloidosis models.
Limitations
- The paper states no explicit limitations.
- Evident from the text: the evidence is conflicting — Fryer et al. found LDLR deletion had no effect on amyloid deposition in huAPP transgenic mice, and Katsouri and Georgopoulos found LDLR's effect on amyloid deposition did not involve ApoE, leaving the mechanism unclear.
- Evident from the text: the therapeutic proposals (statins, tamoxifen, gemfibrozil, glial LDLR elevation) are speculative and described as requiring novel investigations; no efficacy data in amyloidosis models are presented.
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Claims the paper makes
0 of 37 cited sources checked · 0 supported · 0 flagged
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Middle-aged patients with familial hypercholesterolemia exhibit a particularly high incidence of mild cognitive impairment.
“Daniel Zamb on and colleagues [1] recently reported that middle-aged patients with FH exhibit a particularly high incidence of mild cognitive impairment (MCI), a transitional state between the cognitive decline observed in the elderly and proper dementia.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Mild cognitive impairment in familial hypercholesterolemia patients occurs without cerebrovascular disease.
“This latter observation agrees with previous clinical data reported by Zamb on and colleagues [1] regarding the observation of MCI without cerebrovascular disease in FH patients.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Increased susceptibility to amyloid-β-induced neurotoxicity is expected in the case of LDLR dysfunction because amyloid-β uptake and clearance might be impaired.
“Consequently, one might also expect increased susceptibility to Ab-induced neurotoxicity in the case of LDLR dysfunction because Ab uptake and clearance might be impaired in this context.”
Quote in the paperSubstantial claim- Rests on an assumption: Continuous removal of amyloid-β species from the brain into the blood is important for preventing potentially neurotoxic accumulations in interstitial fluid.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Mouse models of familial hypercholesterolemia (ApoB100/LDLr−/− and LDLr−/−) corroborate the observation of mild cognitive impairment.
“Of note, Ramirez and colleagues [2] and we [3] corroborated this observation in ApoB100/LDLr À/À and LDLr À/À experimental mouse models of FH, respectively.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [2]
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- cites [3]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Middle-aged LDLr−/− mice did not show signs of stroke-related features.
“Moreover, we did not observe signs of stroke-related features in middleaged LDLr À/À mice [3].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
LDLR plays an important role in pathways that modulate amyloid-β metabolism.
“Notably, a series of elegant studies have shown that LDLR plays an important role in pathways that modulate amyloid-b (Ab) metabolism.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [4]
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- cites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [6]
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- Interpretationcitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
LDLR can regulate amyloid-β levels.
“Taken together, all of these findings clearly indicate that LDLR can regulate Ab levels.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Overexpression of LDLR in amyloid precursor protein transgenic mice markedly reduces amyloid plaque formation.
“Conversely, Kim and colleagues [5] demonstrated a marked reduction of amyloid plaque formation in the brains of amyloid precursor protein (APP) transgenic mice that overexpress LDLR.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationcitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
LDLR is a pathway for mediating the cellular regulation of amyloid-β levels.
“Taken together, these studies have identified LDLR as a pathway for mediating the cellular regulation of Ab levels and provided evidence that increasing LDLR levels may promote Ab degradation within the brain.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [6]
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- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Amyloid-β can directly bind to LDLR.
“In their study, Basak and colleagues [6] provided evidence that Ab can directly bind to LDLR, suggesting that an interaction between LDLR and Ab could be responsible for LDLR-mediated Ab uptake.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
LDLR overexpression decreases amyloid deposition by altering the steady-state concentration of amyloid-β in brain interstitial fluid.
“Kim and colleagues [5] demonstrated that LDLR overexpression decreases amyloid deposition by altering the steady-state concentration of Ab in the brain interstitial fluid (ISF).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationcitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
LDLR affects amyloid-β metabolism by promoting its clearance from the brain into blood.
“As a result, one could conclude that LDLR affects Ab metabolism by promoting its clearance from the brain into blood [8].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
LDLR plays a unique role in blood-brain barrier-mediated amyloid-β clearance.
“Notably, Castellano and colleagues [8] used a brain efflux index method to demonstrate a unique role for LDLR in the blood-brain barrier (BBB)-mediated Ab clearance.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
LDLR deletion has no impact on APP processing and production of α and β carboxy terminal fragments in mouse brain.
“Katsouri and Georgopoulos [4] also found that LDLR deletion had no impact on APP processing and production of a and b carboxy terminal fragments in the mouse brain.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Deletion of LDLR decreases amyloid-β uptake.
“Deletion of LDLR caused a decrease in Ab uptake, whereas increased LDLR expression significantly enhanced both Ab uptake and clearance [6].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationcitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Interaction between LDLR and amyloid-β could be responsible for LDLR-mediated amyloid-β uptake.
“In their study, Basak and colleagues [6] provided evidence that Ab can directly bind to LDLR, suggesting that an interaction between LDLR and Ab could be responsible for LDLR-mediated Ab uptake.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
LDLR overexpression significantly increases the appearance rate of endogenously produced human amyloid-β from the brain in the blood.
“Specifically, these authors found that LDLR overexpression significantly increased the appearance rate of endogenously produced human Ab (from the brain) in the blood.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Absence of LDLR potentiates amyloid-β-induced neurotoxic effects in mice.
“In this regard, we recently observed that the absence of LDLR potentiated the Ab-induced neurotoxic effects in mice [9].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
LDLR promotes uptake of amyloid-β into primary astrocytes even in ApoE−/− cells.
“Moreover, Basak and colleagues [6] found that LDLR is capable of promoting the uptake of Ab into primary astrocytes even in ApoE À/À cells.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
LDLR deletion had no effect on amyloid deposition in huAPP transgenic mice.
“Nonetheless, it is important to note that in a study by Fryer and colleagues [7], LDLR deletion had no effect on amyloid deposition in huAPP transgenic mice.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [7]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Modulation of LDLR levels alters both amyloid-β uptake and degradation by astrocytes.
“Accordingly, Basak and colleagues [6] demonstrated that modulation of the LDLR levels altered both Ab uptake and degradation by astrocytes.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationcitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Increasing LDLR levels may promote amyloid-β degradation within the brain.
“Taken together, these studies have identified LDLR as a pathway for mediating the cellular regulation of Ab levels and provided evidence that increasing LDLR levels may promote Ab degradation within the brain.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [5]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Some compounds including tamoxifen, statins, and gemfibrozil increase hepatic LDLR levels.
“In this context, some compounds, including tamoxifen, statins, and gemfibrozil [10], have been found to increase the hepatic LDLR levels; therefore, the use of such compounds is incumbent upon novel investigations on their therapeutic potentials in experimental models of amyloidosis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?
Lack of LDLR aggravated amyloid deposition in a transgenic mouse model of Alzheimer's disease.
“On one hand, Katsouri and Georgopoulos [4] reported that a lack of LDLR aggravated amyloid deposition in a transgenic mouse model of AD.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- It may state two separate claims as one. 5
It may state two separate claims as one.
Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?Increased LDLR expression enhances both amyloid-β uptake and clearance.
“Deletion of LDLR caused a decrease in Ab uptake, whereas increased LDLR expression significantly enhanced both Ab uptake and clearance [6].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
It may state two separate claims as one.
Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?Amyloid-β40 and amyloid-β42 bind to the extracellular domain of LDLR with KD values of 47.4 and 37.4 nM, respectively.
“Specifically, the authors showed via immunoprecipitation and surface plasmon resonance that both Ab 40 and Ab 42 could bind to the extracellular domain of LDLR with K D values of 47.4 and 37.4 nm, respectively [6].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
It may state two separate claims as one.
Premiseown data§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?Middle-aged LDLr−/− mice exhibited working, spatial reference, and procedural memory impairments without alterations in exploratory activities and anxiety-related responses.
“Specifically, we found that middle-aged LDLr À/À mice exhibited working, spatial reference, and procedural memory impairments without alterations in exploratory activities and anxiety-related responses.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
It may state two separate claims as one.
Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?In 5XFAD/ApoE−/− LDLr−/− mice compared to 5XFAD/ApoE−/− mice, LDLR might be involved in a mechanism affecting amyloid deposition, whereas ApoE was not involved.
“Notably, these researchers found that LDLR might be involved in a mechanism affecting amyloid deposition, whereas ApoE was not involved.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
It may state two separate claims as one.
Premisecitation§ Low-density Lipoprotein Receptor: A Promising Therapeutic Target to Promote Cerebral Beta-amyloid Clearance?LDLr−/− mice treated with amyloid-β1-40 via acute intracerebroventricular injection presented increased astrogliosis, oxidative stress, and cell permeability in the hippocampus compared to wild-type mice.
“Specifically, LDLr À/À mice treated with Ab 1-40 peptide via acute intracerebroventricular injection presented with increased astrogliosis, oxidative stress, and cell permeability within the hippocampus in comparison with identically treated wild-type C57Bl/6 mice.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
The paper relies on this without support.
Continuous removal of amyloid-β species from the brain into the blood is important for preventing potentially neurotoxic accumulations in interstitial fluid.
“It is worth noting that the continuous removal of Ab species from the brain into the blood is important for preventing potentially neurotoxic accumulations in ISF.”
Citations
Cites
Kim, J., Castellano, J. M., Jiang, H., Basak, J. M., Parsadanian, M., Pham, V., Mason, S. M., Paul, S. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.11.013 · Cited by 274
Basak, J. M., Verghese, P. B., Yoon, H., Kim, J., & Holtzman, D. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.288746 · Cited by 192
Castellano, J. M., Deane, R., Gottesdiener, A. J., Verghese, P. B., Stewart, F. R., West, T., Paoletti, A. C., Kasper, T. R., DeMattos, R. B., Zlokovic, B. V., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206446109 · Cited by 154
Fryer, J. D., DeMattos, R. B., McCormick, L. M., O'Dell, M. A., Spinner, M. L., Bales, K. R., Paul, S. M., Sullivan, P. M., Parsadanian, M., Bu, G., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502143200 · Cited by 139
Higher Incidence of Mild Cognitive Impairment in Familial Hypercholesterolemia
Zambón, D., Quintana, M., Mata, P., Alonso, R., Benavent, J., Cruz-Sánchez, F., Gich, J., Pocoví, M., Civeira, F., Capurro, S., et al. (2010) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.08.015 · Cited by 125
Katsouri, L., & Georgopoulos, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021880 · Cited by 72
Moreira, E. L. G., de Oliveira, J., Nunes, J. C., Santos, D. B., Nunes, F. C., Vieira, D. S. C., Ribeiro-do-Valle, R. M., Pamplona, F. A., de Bem, A. F., Farina, M., et al. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-120541 · Cited by 64
Self-citationde Oliveira, J., Moreira, E. L. G., dos Santos, D. B., Piermartiri, T. C., Dutra, R. C., Pinton, S., Tasca, C. I., Farina, M., Prediger, R. D. S., & de Bem, A. F. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-132228 · Cited by 62
Self-citationRamírez, C., Sierra, S., Tercero, I., Vázquez, J. A., Pineda, A., Manrique, T., & Burgos, J. S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022712 · Cited by 31
Goto, D., Okimoto, T., Ono, M., Shimotsu, H., Abe, K., Tsujita, Y., & Kuwano, M. (1997) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.17.11.2707 · Cited by 23
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Metadata
- Authors
- de Oliveira, J., de Bem, A. F., & Moreira, E. L. G.
- Affiliations
- Universidade Federal de Santa Catarina (BR)
- Departamento de Bioquímica Universidade Federal de Santa Catarina Florianópolis Brazil
- Corresponding author
- Moreira, Eduardo Luiz Gasnhar
- Venue
- CNS Neuroscience & Therapeutics
- Publisher
- Wiley
- Published
- 2014-08-04
- Volume
- 20
- Issue
- 9
- Pages
- 877-878
- ISSN
- 1755-5930 (ISSN-L)
- 1755-5949
- PMC
- PMC6493077
- OpenAlex
- W2025726537
- Cited by
- 0
- References
- 10
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- CNS Neuroscience & Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- LDL receptor, amyloid-beta clearance, Alzheimer's disease, familial hypercholesterolemia, mild cognitive impairment, amyloid-beta metabolism, amyloid plaque formation, memory impairment, therapeutic target, cholesterol metabolism, atherosclerosis, coronary artery disease, APOE ε4, APOE2
- MeSH terms
- Alzheimer Disease, Animals, Cerebral Cortex, Humans, Receptors, LDL, Amyloid beta-Peptides, Mice
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