Estibaliz Capetillo-Zarate

Estibaliz Capetillo-Zarate
Weill Cornell Medical College | Cornell · Department of Biochemistry

Ph.D.

About

62
Publications
5,304
Reads
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2,326
Citations
Additional affiliations
February 2012 - present
Weill Cornell Medical College
Position
  • Reserach Associate
February 2007 - January 2012
Weill Cornell Medical College
Position
  • PostDoc Position
January 2003 - January 2007
Rheinische Friedrich-Wilhelms-Universität Bonn
Position
  • PhD Student

Publications

Publications (62)
Article
Full-text available
Evidence suggests that lightly myelinated cortical regions are vulnerable to aging and Alzheimer’s disease (AD). However, it remains unknown whether plasma markers of amyloid and neurodegeneration are related to deficits in intracortical myelin content, and whether this relationship, in turn, is associated with altered patterns of resting-state fun...
Article
Full-text available
Glial cells are essential to understand Alzheimer’s disease (AD) progression, given their role in neuroinflammation and neurodegeneration. There is a need for reliable and easy to manipulate models that allow studying the mechanisms behind neuron and glia communication. Currently available models such as co-cultures require complex methodologies an...
Article
Full-text available
Amyloid beta (Aβ)-mediated synapse dysfunction is an early event in Alzheimer’s disease (AD) pathogenesis and previous studies suggest that NMDA receptor (NMDAR) dysregulation may contribute to these pathological effects. Although Aβ peptides impair NMDAR expression and activity, the mechanisms mediating these alterations in the early stages of AD...
Article
Introduction Blood and cerebrospinal fluid represent emerging candidate fluids for biomarker identification in Parkinson's disease (PD). Methods We studied 8 individuals carrying the E46K-SNCA mutation (3 PD dementia (PDD), 1 tremor-dominant PD, 2 young rigid-akinetic PD and 2 asymptomatic) and 8 age- and sex-matched healthy controls. We quantifie...
Preprint
Glial cells are essential to understand Alzheimer’s disease (AD) progression, given their role in neuroinflammation and neurodegeneration. There is a need for reliable and easy to manipulate models that allow studying the mechanisms behind neuron and glia communication. Currently available models such as cocultures require complex methodologies and...
Preprint
Microglial phagocytosis is rapidly emerging as a therapeutic target in neurodegenerative and neurological disorders. An efficient removal of cellular debris is necessary to prevent buildup damage of neighbor neurons and the development of an inflammatory response. As the brain professional phagocytes, microglia are equipped with an array of mechani...
Article
Full-text available
Background: Although Alzheimer's disease (AD) is associated with alterations of the central nervous system, this disease has an echo in blood that might represent a valuable source of biomarkers for improved diagnosis, prognosis and for monitoring drug response. Methods: We performed a targeted transcriptomics study on 38 mild Alzheimer's diseas...
Article
Full-text available
Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the diffe...
Chapter
In Alzheimer’s disease (AD), amyloid β peptide (Aβ) causes mitochondrial alterations including disrupted metabolism and dynamics, enhanced oxidative stress, aberrant calcium signaling, and neuronal apoptosis. Natural polyphenols boost mitochondria and bioenergetic function as well as exhibit neuroprotective effects in experimental paradigms that ar...
Preprint
Full-text available
Background Amyloid beta (Aβ)-mediated synapse dysfunction is an early event in Alzheimer's disease (AD) pathogenesis and previous studies suggest that NMDA receptor (NMDAR) dysregulation may contribute to these pathological effects. Although Aβ peptides impair NMDAR expression and activity, the mechanisms mediating these alterations in early stages...
Article
Full-text available
The normal role of Alzheimer's disease (AD)-linked amyloid precursor protein (APP) in the brain remains incompletely understood. Previous studies have reported that lack of APP has detrimental effects on spines and electrophysiological parameters. APP has been described to be important in synaptic pruning during development. The effect of APP knock...
Article
Full-text available
Synapse loss is an early manifestation of pathology in Alzheimer’s disease (AD) and is currently the best correlate to cognitive decline. Microglial cells are involved in synapse pruning during development via the complement pathway. Moreover, recent evidence points towards a key role played by glial cells in synapse loss during AD. However, furthe...
Article
Full-text available
Amyloid beta (Aβ)-mediated ROS overproduction disrupts intra-neuronal redox balance and exacerbates mitochondrial dysfunction which leads to neuronal injury. Polyphenols have been investigated as therapeutic agents that promote neuroprotective effects in experimental models of brain injury and neurodegenerative diseases. The aim of this study was t...
Article
Although dendritic cells are known to play a role in atherosclerosis, few studies have examined the contribution of the wide variety of dendritic cell subsets. Accordingly, their roles in atherogenesis remain largely unknown. We investigated the ability of different dendritic cell subsets to become foam cells after contact with aggregated low-densi...
Article
Full-text available
Pathologic aggregation of β-amyloid (Aβ) peptide and the axonal microtubule-associated protein tau protein are hallmarks of Alzheimer's disease (AD). Evidence supports that Aβ peptide accumulation precedes microtubule-related pathology, although the link between Aβ and tau remains unclear. We previously provided evidence for early co-localization o...
Data
MAP2 reduction in stratum lacunosum-moleculare (SLM) by immunoperoxidase labeling. Immunoreactivity for MAP2 was reduced in CA1 SLM of these representative 18-month-old Tg2576 (18 mo Tg) mice compared to age-matched wild-type (18 mo WT) mice (n = 3). Scale bar: 50 µm. (EPS)
Data
(A) Immuno-EM showing gold-particles of Aβ42 (using antibody AB5078P) are associated with the outer membrane of a MVB (arrows) close to the Golgi apparatus in an 11-month-old wild-type mouse brain, while no gold-particles are evident in the Golgi apparatus, in which full-length APP and APP CTFs (C-terminal fragments) are known to primarily reside....
Data
Accumulation of M/LMW Aβ42 peptides in tau-1-positive axons. (A) Immunofluorescent labeling of Tg2576 (top) and wild-type (bottom) mouse cortices revealed little M/LMW Aβ42 peptide co-localization (arrowheads) with tau-1-positive axons at 17 months of age, which was slightly more apparent in Tg2576 mice (n = 3). Bar: 20 µm. (B) More Aβ42 peptide ac...
Article
Soluble amyloid β-protein (Aβ) aggregates have been identified in the Alzheimer's disease (AD) brain. Dispersed Aβ aggregates in the brain parenchyma are different from soluble, membrane-associated and plaque-associated solid aggregates. They are in mixture with the extra- or intracellular fluid but can be separated from soluble proteins by ultrace...
Article
Full-text available
An early role of amyloid-β peptide (Aβ) aggregation in Alzheimer's disease pathogenesis is well established. However, the contribution of intracellular or extracellular forms of Aβ to the neurodegenerative process is a subject of considerable debate. We here describe transgenic mice expressing Aβ1-40 (APP47) and Aβ1-42 (APP48) with a cleaved signal...
Article
β-Amyloid (Aβ) plaques are a pathological hallmark of Alzheimer's disease (AD) and multiple lines of evidence have linked Aβ with AD. However, synapse loss is known as the best pathological correlate of cognitive impairment in AD, and intraneuronal Aβ accumulation has been shown to precede plaque pathology. The progression of Aβ accumulation to syn...
Article
Full-text available
A central question in Alzheimer's disease (AD) research is what role β-amyloid peptide (Aβ) plays in synaptic dysfunction. Synaptic activity increases Aβ secretion, potentially inhibiting synapses, but also decreases intraneuronal Aβ, protecting synapses. We now show that levels of secreted Aβ fall with time in culture in neurons of AD-transgenic m...
Article
β-Amyloid (Aβ) accumulation and aggregation are hallmarks of Alzheimer's disease (AD). High-resolution three-dimensional (HR-3D) volumetric imaging allows for better analysis of fluorescence confocal microscopy and 3D visualization of Aβ pathology in brain. Early intraneuronal Aβ pathology was studied in AD transgenic mouse brains by HR-3D volumetr...
Article
Full-text available
Incomplete lysosomal acidification in microglia inhibits the degradation of fibrillar forms of Alzheimer's amyloid β peptide (fAβ). Here we show that in primary microglia a chloride transporter, ClC-7, is not delivered efficiently to lysosomes, causing incomplete lysosomal acidification. ClC-7 protein is synthesized by microglia but it is mistarget...
Article
Full-text available
Accumulation of β-amyloid (Aβ) and loss of synapses are hallmarks of Alzheimer's disease (AD). How synaptic activity relates to Aβ accumulation and loss of synapses is a current topic of major interest. Synaptic activation promotes Aβ secretion, and chronic reduction of synaptic activity reduced Aβ plaques in an AD transgenic mouse model. This sugg...
Data
(A) HFS induced normal LTP in slices from 2-month-old Tg2576 mice, comparing to WT mice. n = 4. (B) Western blotting showed no reduction of phospho-p70S6K and PSD95 in slice from 2-month-old Tg2576 mice. n = 4. (2.73 MB TIF)
Data
(A) Weak HFS (one train) induced similar early LTP in slices from 3–4-month-old Tg2576 mice and WT mice that decayed to baseline in about 80 minutes. n = 5. (B) Slices from 3–4-month-old Tg2576 mice demonstrated normal PPF. n = 5. Scale bar, 0.5 mV/25 ms. (2.56 MB TIF)
Data
Increased labeling of phospho-p70SK6 in AD vulnerable neurons of the hippocampus in a case with AD (A) compared to a control (B). Inserts represent higher power views of the black boxes within the lower power images. The inset in (A) reveals tangle-like labeling of phospho-p70SK6 in CA1 pyramidal neurons. Scale bar, 1 mm. (8.75 MB TIF)
Article
Full-text available
The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase that plays a pivotal role in multiple fundamental biological processes, including synaptic plasticity. We explored the relationship between the mTOR pathway and β-amyloid (Aβ)-induced synaptic dysfunction, which is considered to be critical in the pathoge...
Article
Full-text available
The aberrant accumulation of aggregated beta-amyloid peptides (Abeta) as plaques is a hallmark of Alzheimer's disease (AD) neuropathology and reduction of Abeta has become a leading direction of emerging experimental therapies for the disease. The mechanism(s) whereby Abeta is involved in the pathophysiology of the disease remain(s) poorly understo...
Article
Full-text available
A central question in Alzheimer's disease research is what role synaptic activity plays in the disease process. Synaptic activity has been shown to induce beta-amyloid peptide release into the extracellular space, and extracellular beta-amyloid has been shown to be toxic to synapses. We now provide evidence that the well established synaptotoxicity...
Article
A central question in Alzheimer's disease research is what role synaptic activity plays in the disease process. Synaptic activity has been shown to induce-amyloid peptide release into the extracellular space, and extracellular-amyloid has been shown to be toxic to synapses. We now provide evidence that the well established synaptotoxicity of extrac...
Article
Although beta-amyloid (Abeta) plaques and tau neurofibrillary tangles are hallmarks of Alzheimer's disease (AD) neuropathology, loss of synapses is considered the best correlate of cognitive decline in AD, rather than plaques or tangles. How pathological Abeta and tau aggregation relate to each other and to alterations in synapses remains unclear....
Article
Full-text available
Amyloid-beta-protein (Abeta) is generally assessed by neuropathologists in diagnostics. This BrainNet Europe ( http://www.brainnet-europe.org/ ) (15 centres and 26 participants) study was carried out to investigate the reliability of such an assessment. In the first part of this trial, tissue microarray sections were stained with the antibody of ea...
Article
The role of cerebral amyloid angiopathy (CAA) in the pathogenesis of Alzheimer's disease (AD) is not fully understood. Here, we studied whether CAA is associated with alterations in microvascularisation in transgenic mouse models and in the human brain. APP23 mice at 25-26 months of age exhibited severe CAA in thalamic vessels whereas APP51/16 mice...
Article
Full-text available
Argyrophilic grain disease (AGD), a neurodegenerative disorder, is often associated with mild to moderate Alzheimer's disease (AD)-related pathology. The development of dementia in AGD is associated with the extent of coexisting AD-related pathology. Therefore, the question arises whether the degenerative changes in the neuronal network of demented...
Article
The deposition of the amyloid beta-protein (Abeta) is a hallmark of Alzheimer's disease (AD). One reason for Abeta-accumulation and deposition in the brain may be an altered drainage along perivascular channels. Extracellular fluid is drained from the brain towards the cervical lymph nodes via perivascular channels. The perivascular space around ce...
Article
Full-text available
Vesicular release of neurotransmitter is the universal output signal of neurons in the brain. It is generally believed that fast transmitter release is restricted to nerve terminals that contact postsynaptic cells in the gray matter. Here we show in the rat brain that the neurotransmitter glutamate is also released at discrete sites along axons in...
Article
Full-text available
The amyloid beta-protein (Abeta) is the main component of Alzheimer's disease-related senile plaques. Although Abeta is associated with the development of Alzheimer's disease, it has not been shown which forms of Abeta induce neurodegeneration in vivo and which types of neurons are vulnerable. To address these questions, we implanted DiI crystals i...
Article
The deposition of amyloid beta protein (Abeta) in the human brain and the generation of neurofibrillary tangles are the histopathological hallmarks of Alzheimer's disease. Accumulation of Abeta takes place in senile plaques and in cerebrovascular deposits as a result of an imbalance between Abeta production and clearance. This Review describes the...
Article
Full-text available
Different types of amyloid beta-protein (Abeta)-containing plaques occur in brains of Alzheimer's disease (AD) patients. Diffuse plaques seen during early stages of AD differ from neuritic plaques in later stages both with respect to the length of the Abeta peptides and the presence of other proteins, e.g., apolipoprotein-E (apoE). Since apoE is in...
Article
Different types of senile plaques occur in brains of Alzheimer’s disease (AD) patients. Senile plaques seen in early preclinical stages of AD differ from those in clinical stages both in their composition of Aβ-peptides of different lengths and other proteins, e.g., apoE. ApoE is involved in Aβ-transport and -uptake. Therefore, it is tempting to sp...
Article
A characteristic feature of Alzheimer's disease (AD) is the extracellular deposition of the amyloid β-protein (Aβ). Amyloid precursor protein (APP) transgenic mouse models for AD overexpress mutant APP and show Aβ plaques in the brain. Although neuronal loss has been observed in these mice at advanced stages of Aβ-plaque deposition it remains uncle...

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