Aβ Deposition In Alzheimer's Disease Research Articles

Microglia-derived Galectin-9 drives amyloid-β pathology in Alzheimer's disease.

The accumulation of amyloid-β (Aβ) and overactivation of microglia contribute to the pathogenesis of Alzheimer's disease (AD), but the interaction between microglial activation and Aβ deposition in AD remains elusive. Here we revealed that Aβ activates microglia and promotes the release of Galectin-9 (Gal-9), a member of the β-galactoside-binding family of lectins. The levels of Gal-9 in the cerebrospinal fluid and brain tissues of AD patients are higher than those in control subjects. Gal-9 interacts with Aβ and promotes its aggregation, generating Gal-9-Aβ fibrils with enhanced seeding activity and neurotoxicity. The expression of Gal-9 increases with age in the brains of APP/PS1 transgenic mice. Knockout of Gal-9 in APP/PS1 mice substantially reduced Aβ sedimentation, neuroinflammation, and cognitive impairment. Moreover, depletion of Gal-9 inhibited the seeding activity of brain homogenates from APP/PS1 mice. These findings reveal a mechanism by which microglia-derived Gal-9 accelerates Aβ aggregation and seeding in AD. Thus, strategies aimed at inhibiting Gal-9 may hold promise as a disease-modifying therapy to alleviate AD pathology.

Breviscapine Combined with BMSCs Reduces Aβ Deposition in Rat with Alzheimer's Disease by Regulating Circular RNA ciRS-7.

This study aimed to clarify that breviscapine combined with bone marrow mesenchymal stem cells (BMSCs) treatment can reduce Aβ deposition in Alzheimer's disease (AD) patients. AD is a common degenerative disease of the central nervous system. Aβ protein deposition in the cerebral cortex and hippocampus causes neuronal peroxidation damage, synaptic dysfunction, neuroinflammation, and nerve cell apoptosis, and ultimately leads to AD. To investigate whether breviscapine combined with BMSCs treatment can reduce Aβ deposition in AD. The AD rat model was successfully induced by Aβ1-42. The expression of protein and mRNA was detected by western blot and reverse transcription-quantitative PCR (RT-qPCR), respectively. In AD rat brain tissue, the expression of circular RNA ciRS-7 (ciRS-7), ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), and NF-kappaB p65 was significantly downregulated, and the expression of β-amyloid precursor protein (APP), β-site APPcleaving enzyme 1 (BAEC1), and Aβ was upregulated. The expression of ciRS-7, UCHL1, and p65 was significantly upregulated after breviscapine or BMSCs treatment, and there was increased APP and BAEC1 degradation. Notably, breviscapine combined with BMSCs treatment was more effective than either treatment alone. In SH-SY5Y cells, overexpression of ciRS-7 reduced Aβ deposition by upregulating UCHL1 to degrade APP and BAEC1, but these effects were reversed with inhibition of NF-kB signaling. Finally, knockdown of ciRS-7 elevated Aβ, APP, and BAEC1 expression in each group of rats compared with the control. Breviscapine combined with BMSCs treatment can reduce Aβ deposition in AD rats and promote the degradation of APP and BAEC1 by activating NF-kB to promote UCHL1 expression.

Mesenchymal Stem Cells Improve Cognitive Impairment and Reduce Aβ Deposition via Promoting AQP4 Polarity and Relieving Neuroinflammation in Rats With Chronic Hypertension-Induced Cerebral Small-Vessel Disease.

Cerebral small-vessel disease (CSVD) is the main cause of vascular cognitive impairment (VCI), and the accumulation of amyloid β-protein (Aβ) may be significantly involved in CSVD-induced VCI. The imbalance between Aβ production and clearance is believed to be an important pathological mechanism of Aβ deposition in Alzheimer disease. In this study, we aimed to disclose the roles of aquaporin 4 (AQP4) and neuroinflammation in CSVD, which were the key factors for Aβ clearance and production, respectively, and the effect of mesenchymal stem cells (MSCs) on Aβ deposition and these two factors. The stroke-prone renovascular hypertensive (RHRSP) rats were grouped and received MSC and MSC + AS1517499 (an inhibitor of pSTAT6). The latter was used to explore the underlying mechanism. The cognitive function, white matter lesions, Aβ expression, expression, and polarity of AQP4, neuroinflammation and the STAT6 pathway were investigated. Compared with sham-operated rats, RHRSP rats showed spatial cognitive impairment, white matter lesions and Aβ deposition. Moreover, AQP4 polarity disorder and neuroinflammatory activation were found, which were linked to Aβ deposition. Treatment with MSCs markedly improved cognitive tasks and reduced Aβ deposition but failed to reduce white-matter lesions. Furthermore, MSCs not only promoted AQP4 polarity but also alleviated neuroinflammation probably through the STAT6 pathway. The present study demonstrated that Aβ deposition, AQP4 polarity disorder and neuroinflammation might be involved in CSVD and the regulatory effects of MSCs on them suggested potential therapeutic value for CSVD.

Association of Aß deposition and regional synaptic density in early Alzheimer's disease: a PET imaging study with [11C]UCB-J

<h3>Introduction</h3> Synaptic loss is an early pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. We have recently demonstrated extensive synaptic loss in the medial temporal and neocortical regions of participants with AD, using <i>in vivo</i> positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A), a promising biomarker of synaptic density. Attempts to associate amyloid-β (Aβ) pathogenesis with synaptic loss in AD however, have thus far been limited to small numbers of postmortem studies. Aβ plaque burden is not well-correlated with indices of clinical severity or neurodegeneration—at least in the dementia stage—as deposition of Aβ reaches a ceiling. In this study, we examined in vivothe association between fibrillar Aβ deposition and synaptic density in early AD using [¹¹C]PiB and [¹¹C]UCB-J PET. We hypothesized that global Aβ deposition would be more strongly inversely associated with hippocampal synaptic density in participants with amnestic mild cognitive impairment (aMCI, a stage of continued Aβ accumulation) compared to those with dementia (a stage of relative Aβ plateau). <h3>Methods</h3> [¹¹C]UCB-J (for SV2A) and [¹¹C]PiB (Aβ deposition) binding were measured in 14 participants with aMCI due to AD, 24 participants with mild AD dementia, and 19 cognitively normal (CN) participants aged 55-85 years. For [¹¹C]PiB data analysis, parametric images of binding potential (<i>BP</i>_ND) were generated using SRTM2 with cerebellum as a reference region and converted to distribution volume ratios (<i>DVR</i>). For [¹¹C]UCB-J, <i>BP</i>_NDwas computed using SRTM2 with a shrunken centrum semiovale reference region and converted to <i>DVR</i> with a cerebellum reference region. For the primary analysis of the association between global Aβ deposition and hippocampal SV2A binding in participants with aMCI and dementia, separate univariate regression analyses were performed for each diagnostic group with Pearson <i>r</i> and associated two-tailed <i>P</i> values reported for each model. Fisher <i>z</i>-transformation assessed significant differences in correlation coefficients between the aMCI and dementia groups, with one-tailed <i>P</i> values reported. Exploratory analyses examined correlations between both global and regional Aβ deposition and SV2A binding across a broad range of brain regions using both ROI- and surface-based approaches. Global Aβ deposition was determined for a composite of regions commonly affected by Aβ deposition in AD which included: prefrontal, lateral temporal, posterior cingulate/precuneus, and lateral parietal ROIs. <h3>Results</h3> The AD group showed significant widespread reductions in cortical and subcortical synaptic density, most pronounced in the medial temporal lobe, and significantly elevated cortical amyloid in regions commonly affected by AD pathology (Figure 1). We observed a significant inverse association between global Aβ deposition and hippocampal SV2A binding in participants with aMCI (r = -0.55, <i>P</i> = 0.04), but not mild dementia (r = 0.05, <i>P</i> = 0.82; difference statistically significant by Fisher <i>z</i>= -1.80, <i>P</i> = 0.04; Figure 2).This stronger association was observed to survive partial volume correction (aMCI <i>r</i>= -0.56, <i>P</i>= 0.04; dementia <i>r</i>= -0.01, <i>P</i>= 0.96; Fisher <i>z</i>= -1.67, <i>P</i>= 0.047). Exploratory analyses across other ROIs and whole brain analyses demonstrated no broad or consistent associations between global Aβ deposition and regional SV2A binding in either diagnostic group. ROI-based analyses of the association between regional Aβ deposition and SV2A binding also revealed no consistent pattern but suggested a nominal inverse association in the dementia group between local Aβ deposition and SV2A binding in medial occipital cortex and a more compelling, larger positive correlation between local Aβ accumulation and synaptic density in hippocampus (Table 1). <h3>Conclusions</h3> To our knowledge, we have conducted the first <i>in vivo</i> study investigating the relationship between Aβ deposition and synaptic alterations in participants with AD. We observed significant inverse associations between measures of global Aβ deposition and hippocampal synaptic density within participants with aMCI but not with dementia. Our findings lend support to a model in which fibrillar Aβ may still accumulating in the early stages of clinical disease but approaching a relative plateau, a point at which Aβ may uncouple from neurodegenerative processes including synaptic loss. Future research shouldinvestigate the relationship between Aβ deposition and synaptic loss in larger cohorts beginning preclinically and followed longitudinally in conjunction with other biomarkers. <h3>Funding</h3> P50-AG047270 (CHvD), P30-AG066508 [CHvD], K23-AG057794 (APM), R01-AG052560 (REC, CHV), R01-AG062276 (CHvD), Dana Foundation (MKC), T32-MH019961 (RSO), and Thomas P. Detre Fellowship (RSO).

Interaction between tissue transglutaminase and amyloid-beta: Protein-protein binding versus enzymatic crosslinking

Self-interaction, chaperone binding and posttranslational modification of amyloid-beta (Aβ) is essential in the initiation and propagation of Aβ aggregation. Aggregation results in insoluble Aβ deposits characteristic of Alzheimer's disease (AD) brain lesions, i.e. senile plaques and cerebral amyloid angiopathy. Tissue transglutaminase (tTG) is a calcium-dependent enzyme that catalyzes posttranslational modifications including the formation of covalent ε-(γ-glutamyl)lysine isopeptide bonds (molecular crosslinks), and colocalizes with Aβ deposits in AD. Two independent groups recently found that apart from the induction of Aβ oligomerization, the blood-derived transglutaminase member FXIIIa forms stable protein-protein complexes with Aβ independent of the transamidation reaction. Here, we investigated whether also tTG forms rigid protein complexes with Aβ in the absence of catalytic activation. We found that both Aβ1-40 and Aβ1-42 are substrates for tTG-catalyzed crosslinking. In addition, in the absence of calcium or the presence of a peptidergic inhibitor of tTG, stable tTG-Aβ1-40 complexes were found. Interestingly, the stable complexes between tTG and Aβ1-40, were only found at ‘physiological’ concentrations of Aβ1-40. Together, our data suggest that depending on the Aβ species at hand, and on the concentration of Aβ, rigid protein-complexes are formed between tTG and Aβ1-40 without the involvement of the crosslinking reaction.

Transplantation of in vitro cultured endothelial progenitor cells repairs the blood-brain barrier and improves cognitive function of APP/PS1 transgenic AD mice

To date, the pathogenesis of Alzheimer's disease (AD) remains unclear. It is well-known that excessive deposition of Aβ in the brain is a crucial part of the pathogenesis of AD. In recent years, the AD neurovascular unit hypothesis has attracted much attention. Impairment of the blood-brain barrier (BBB) leads to abnormal amyloid-β (Aβ) transport, and chronic cerebral hypoperfusion causes Aβ deposition throughout the onset and progression of AD. Endothelial progenitor cells (EPCs) are the universal cells for repairing blood vessels. Our previous studies have shown that a reduced number of EPCs in the peripheral blood results in cerebral vascular repair disorder, cerebral hypoperfusion and neurodegeneration, which might be related to the cognitive dysfunction of AD patients. This study was designed to confirm whether EPCs transplantation could repair the blood-brain barrier, stimulate angiogenesis and reduce Aβ deposition in AD. The expression of ZO-1, Occludin and Claudin-5 was up-regulated in APP/PS1 transgenic mice after hippocampal transplantation of EPCs. Consistent with previous studies, EPC transplants also increased the microvessel density. We observed that Aβ senile plaque deposition was decreased and hippocampal cell apoptosis was reduced after EPCs transplantation. The Morris water maze test showed that spatial learning and memory functions were significantly improved in mice transplanted with EPCs. Consequently, EPCs could up-regulate the expression of tight junction proteins, repair BBB tight junction function, stimulate angiogenesis, promote Aβ clearance, and decrease neuronal loss, ultimately improve cognitive function. Taken together, these data demonstrate EPCs may play an important role in the therapeutic implications for vascular dysfunction in AD.

Editorial: Alzheimer's Disease and the Fornix.

The fornix is a white matter bundle that connects the hippocampus with other limbic structures. It appears in the literature as early as 1543 in a historical publication of De Humani Corporis Fabrica by Andreas Vesalius (Swanson, 2014). The fornix is important for episodic memory recall (Tsivilis et al., 2008), which is impaired in Alzheimer's disease (AD). Alterations in the fornix were first observed in post-mortem AD brains (Hopper and Vogel, 1976). This volume focuses on the role of the fornix, and other limbic fibers, in the disease mechanisms of AD with some attention to how this might be applied in clinical practice.

Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy.

Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy.

Identification of N-Terminally Truncated Pyroglutamate Amyloid-β in Cholesterol-Enriched Diet-Fed Rabbit and AD Brain

The main amyloid-β peptide (Aβ) variants detected in the human brain are Aβ1-40 and Aβ1-42; however, a significant proportion of Aβ in Alzheimer's disease (AD) brain also consists of N-terminal truncated/modified species. AβN3(pE), Aβ peptide bearing amino-terminal pyroglutamate at position 3, has been demonstrated to be a major N-truncated/modified constituent of intracellular, extracellular, and vascular Aβ deposits in AD and Down syndrome brain tissue. It has been previously demonstrated that rabbits fed a diet enriched in cholesterol and given water containing trace copper levels developed AD-like pathology including intraneuronal and extracellular Aβ accumulation, tau hyperphosphorylation, vascular inflammation, astrocytosis, microgliosis, reduced levels of acetylcholine, as well as learning deficits and thus, may be used as a non-transgenic animal model of sporadic AD. In the present study, we have demonstrated for the first time the presence of AβN3(pE) in blood vessels in cholesterol-enriched diet-fed rabbit brain. In addition, we detected AβN3(pE) immunoreactivity in all postmortem AD brain samples studied. We believe that our results are potentially important for evaluation of novel therapeutic molecules/strategies targeting Aβ peptides in a suitable non-transgenic animal model.

Enhanced Antigen Retrieval of Amyloid β Immunohistochemistry

Senile plaques, extracellular deposits of amyloid β peptide (Aβ), are one of the pathological hallmarks of Alzheimer disease (AD). As the standard immunohistochemical detection method for Aβ deposits, anti-Aβ immunohistochemistry combined with antigen retrieval (AR) by formic acid (FA) has been generally used. Here, we present a more efficient AR for Aβ antigen. On brain sections of AD and its mouse model, a double combination of either autoclave heating in EDTA buffer or digestion with proteinase K plus FA treatment reinforced Aβ immunoreactivity. A further triple combination of digestion with proteinase K (P), autoclave heating in EDTA buffer (A), and FA treatment (F), when employed in this order, gave a more enhanced immunoreactivity. Our PAF method prominently visualized various forms of Aβ deposits in AD that have not been clearly detected previously and revealed numerous minute-sized plaques both in AD and the mouse model. Quantification of Aβ loads showed that the AR effect by the PAF method was 1.86-fold (in the aged human brain) and 4.64-fold (in the mouse brain) higher than that by the FA method. Thus, the PAF method could have the potential to be the most sensitive tool so far to study Aβ pathology in AD and its mouse model.

The Contribution of the Amyloid Hypothesis to the Understanding of Alzheimer's Disease: A Critical Overview

The Contribution of the Amyloid Hypothesis to the Understanding of Alzheimer's Disease: A Critical Overview

Small Heat Shock Proteins Induce a Cerebral Inflammatory Reaction

More than 80% of Alzheimer's disease (AD) patients have some degree of cerebral amyloid angiopathy (CAA). In addition to arteries and veins, capillaries can also be affected. Capillary CAA (capCAA), rather than CAA in larger vessels, is associated with flame-like amyloid-beta (Aβ) deposits that may extend beyond the vessel wall and radiate into the neuropil, a phenomenon also known as "dyshoric angiopathy." Aβ deposits in AD, parenchymal as well as (cap)CAA and dyshoric angiopathy, are associated with a local inflammatory reaction, including activation of microglial cells and astrocytes that, among others, produce cytokines and reactive oxygen species. This neuroinflammatory reaction may account for at least part of the cognitive decline. In previous studies we observed that small heat shock proteins (sHsps) are associated with Aβ deposits in AD. In this study the molecular chaperones Hsp20, HspB8 and HspB2B3 were found to colocalize with CAA and capCAA in AD brains. In addition, Hsp20, HspB8 and HspB2B3 colocalized with intercellular adhesion molecule 1 (ICAM-1) in capCAA-associated dyshoric angiopathy. Furthermore, we demonstrated that Hsp20, HspB8 and HspB2B3 induced production of interleukin 8, soluble ICAM-1 and monocyte chemoattractant protein 1 by human leptomeningeal smooth muscle cells and human brain astrocytes in vitro and that Hsp27 inhibited production of transforming growth factor beta 1 and CD40 ligand. Our results suggest a central role for sHsps in the neuroinflammatory reaction in AD and CAA and thus in contributing to cognitive decline.

FK506 Reduces Amyloid Plaque Burden and Induces MMP-9 in AβPP/PS1 Double Transgenic Mice

Deposition of amyloid-β peptide (Aβ) and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Recently, calcineurin (CaN) has been reported as a potential modulator of memory function, synaptic plasticity, and neural degeneration in brains of AD animal models. In the present study, we examined the relationship between Aβ accumulations and CaN activity in brains of the AβPP/PS1 double transgenic mice. Treatment with FK506, a CaN inhibitor, significantly reduces Aβ burden and restores synaptic proteins (synaptophysin and postsynaptic density protein-95; PSD-95) while inducing matrix metallopeptidase-9 (MMP-9) expression in GFAP-positive astrocytes in the brain. These results suggest a role of FK506 and control of CaN activity in neuroprotection associated with Aβ deposition in AD.

Microglial VEGF Receptor Response Is an Integral Chemotactic Component in Alzheimer's Disease Pathology

We hypothesize that microglial chemotactic responses to amyloid-beta peptide (Abeta(1-42)) serve as an early and integral component of inflammatory response in Alzheimer's disease (AD) brain. This study reports a receptor for vascular endothelial growth factor (VEGF), termed VEGF-1 (Flt-1), subserves microglial chemotactic responses induced by Abeta(1-42) stimulation, in vivo and in vitro. Expression of Flt-1 was significantly increased in tissue obtained from AD patients [compared with tissue from nondemented (ND) individuals], in Abeta(1-42)-injected rat hippocampus, and in peptide-stimulated human microglia. Single and double immunohistochemical staining demonstrated marked immunoreactivity, for both Flt-1 and its ligand VEGF, in association with microglia and Abeta deposits in AD, but not ND, brain tissue. Functionally, treatment with anti-Flt-1 antibody was highly effective in inhibiting microglial mobility and chemotactic responses measured in vitro using a transwell migration assay. In vivo, transplanted enhanced green fluorescent protein (EGFP)-labeled microglia exhibited Flt-1-dependent chemotaxis induced by peptide injection with anti-Flt-1 effective in blocking migration of cells. Importantly, anti-Flt-1 reduction of microglial mobility was neuroprotective in peptide-injected hippocampus and associated with a significant increase in numbers of viable hippocampal neurons. The results of this study suggest critical functional roles for Flt-1 in mediating microglial chemotactic inflammatory responses which contribute to pathological conditions in AD brain.

Age-dependent high-density clustering of GM1 ganglioside at presynaptic neuritic terminals promotes amyloid β-protein fibrillogenesis

The deposition of amyloid β-protein (Aβ) is an invariable feature of Alzheimer's disease (AD); however, the biological mechanism underlying Aβ assembly into fibrils in the brain remains unclear. Here, we show that a high-density cluster of GM1 ganglioside (GM1), which was detected by the specific binding of a novel peptide (p3), appeared selectively on synaptosomes prepared from aged mouse brains. Notably, the synaptosomes bearing the high-density GM1 cluster showed extraordinary potency to induce Aβ assembly, which was suppressed by an antibody specific to GM1-bound Aβ, an endogenous seed for AD amyloid. Together with evidence that Aβ deposition starts at presynaptic terminals in the AD brain and that GM1 levels significantly increase in amyloid-positive synaptosomes prepared from the AD brain, our results suggest that the age-dependent high-density GM1 clustering at presynaptic neuritic terminals is a critical step for Aβ deposition in AD.

Transthyretin Interacts with Metallothionein 2

Transthyretin (TTR) is a 55 kDa homotetrameric protein known for the transport of thyroxine and the indirect transportation of retinol. Within the central nervous system, TTR is primary synthesized and secreted into the cerebral spinal fluid by the choroid plexus (CP), whereas most TTR in the systemic circulation is produced and secreted by the liver. TTR is involved in two types of amyloid disease, the senile systemic amyloidosis and the familial amyloidotic polyneuropathy. TTR has also been implicated in the sequestration of amyloid beta peptide (Abeta), preventing its deposition. To explore other biological roles for TTR, we searched for protein-protein interactions using the yeast two-hybrid system with the full-length human TTR cDNA as bait. We found a novel interaction between TTR and metallothionein 2 (MT2) in human liver. This interaction was confirmed by competition binding assays, co-immunoprecipitation, cross-linking, and Western blotting experiments. Binding studies using MT1 showed a saturable specific interaction with TTR with a Kd of 244.8 +/- 44.1 nM. Western blotting experiments revealed a TTR-MT1/2 protein complex present in rat CP and kidney tissue extracts. Immunofluorescence experiments, in CP primary cell cultures and in CP paraffin sections, showed co-localization of TTR and MT1/2 in the cytoplasm of epithelial CP cells and localization of MT1/2 in the endoplasmic reticulum. Moreover, dot blot immunoassays of rat CSF provided the first evidence, to our knowledge, of circulating metallothionein in CSF. Taken together, we suggest that TTR-MT1/2 complexes may be functionally significant not only in healthy conditions but also in Abeta deposition in Alzheimer disease, thereby providing a novel potential therapeutic target.

Neuroserpin Binds Aβ and Is a Neuroprotective Component of Amyloid Plaques in Alzheimer Disease

Alzheimer disease is characterized by extracellular plaques composed of Abeta peptides. We show here that these plaques also contain the serine protease inhibitor neuroserpin and that neuroserpin forms a 1:1 binary complex with the N-terminal or middle parts of the Abeta(1-42) peptide. This complex inactivates neuroserpin as an inhibitor of tissue plasminogen activator and blocks the loop-sheet polymerization process that is characteristic of members of the serpin superfamily. In contrast neuroserpin accelerates the aggregation of Abeta(1-42) with the resulting species having an appearance that is distinct from the mature amyloid fibril. Neuroserpin reduces the cytotoxicity of Abeta(1-42) when assessed using standard cell assays, and the interaction has been confirmed in vivo in novel Drosophila models of disease. Taken together, these data show that neuroserpin interacts with Abeta(1-42) to form off-pathway non-toxic oligomers and so protects neurons in Alzheimer disease.

Effects of apoE isoforms on beta-amyloid-induced matrix metalloproteinase-9 in rat astrocytes

Matrix metalloproteinase-9 (MMP-9) may play a role in the inflammatory glial response during Alzheimer's disease (AD). Astrocytes can degrade beta-amyloid (Aβ) and extracellular proteolysis via MMP-9 may be involved. Because Apolipoprotein E ( APOE) genotype is an important factor for AD, we ask whether various apoE isoforms can influence Aβ-induced MMP-9 responses in primary rat astrocytes. Our data show that apoE4 significantly dampens Aβ-induced MMP-9 levels, possibly by downregulating the Rho–Rho kinase (ROCK) pathway. Reduction of astrocytic MMP-9 by apoE4 may affect Aβ clearance and promote Aβ deposition in AD.

P3-200: Relationship between neurofibrillary pathology and Aβ deposition in Alzheimer disease

P3-200: Relationship between neurofibrillary pathology and Aβ deposition in Alzheimer disease

P3-176 Lipid rafts, GM1 and Aβ deposits in Alzheimer disease

P3-176 Lipid rafts, GM1 and Aβ deposits in Alzheimer disease