The FGFR3::TACC3 fusion has been reported in subsets of diverse cancers including urothelial and squamous cell carcinomas (SCC). However, the morphology of FGFR3::TACC3-positive head and neck carcinomas has not been well studied and it is unclear if this fusion represents a random event, or if it might characterize a morphologically distinct tumor type. We describe nine FGFR3::TACC3 fusion-positive head and neck carcinomas affecting six males and three females aged 38 to 89 years (median, 59). The tumors originated in the sinonasal tract (n = 4), parotid gland (n = 2), and one case each in the oropharynx, submandibular gland, and larynx. At last follow-up (9-21 months; median, 11), four patients developed local recurrence and/or distant metastases, two died of disease at 11 and 12 months, one died of other cause, one was alive with disease, and two were disease-free. Three of six tumors harbored high risk oncogenic HPV infection (HPV33, HPV18, one unspecified). Histologically, three tumors revealed non-keratinizing transitional cell-like or non-descript morphology with variable mixed inflammatory infiltrate reminiscent of mucoepidermoid or DEK::AFF2 carcinoma (all were HPV-negative), and three were HPV-associated (all sinonasal) with multiphenotypic (1) and non-intestinal adenocarcinoma (2) pattern, respectively. One salivary gland tumor showed poorly cohesive large epithelioid cells with prominent background inflammation and expressed AR and GATA3, in line with a possible salivary duct carcinoma variant. Two tumors were conventional SCC. Targeted RNA sequencing revealed an in-frame FGFR3::TACC3 fusion in all cases. This series highlights heterogeneity of head and neck carcinomas harboring FGFR3::TACC3 fusions, which segregates into three categories: (1) unclassified HPV-negative category, morphologically distinct from SCC and other entities; (2) heterogeneous group of HPV-associated carcinomas; and (3) conventional SCC. A driver role of the FGFR3::TACC3 fusion in the first category (as a potential distinct entity) remains to be further studied. In the light of available FGFR-targeting therapies, delineation of these tumors and enhanced recognition is recommended.

• MeSH
• dlaždicobuněčné karcinomy hlavy a krku virologie   patologie   genetika   MeSH
• dospělí MeSH
• fenotyp MeSH
• fúzní onkogenní proteiny genetika   MeSH
• infekce papilomavirem * patologie   komplikace   genetika   virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory hlavy a krku * patologie   virologie   genetika   MeSH
• proteiny asociované s mikrotubuly genetika   MeSH
• receptor fibroblastových růstových faktorů, typ 3 * genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom patologie   genetika   virologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Plasma phosphorylated tau (p-tau)181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and amyloid beta ratio (Aβ42/40) may have diagnostic and prognostic value in Alzheimer's disease (AD). Here we assess which markers can best identify AD from controls and other non-AD dementias in a large international multi-center study. METHODS: Plasma samples (n = 1298) were collected from six international centers. Aβ40, Aβ42, GFAP, NfL, and p-tau181 were measured using single molecule array. In each group, AD diagnosis/co-pathology was defined according to cerebrospinal fluid biomarkers or amyloid positron emission tomography. Validations were performed in three separate cohorts via single and dual cut-off models. RESULTS: p-tau181 showed the best area under the curve value to separate AD from frontotemporal dementia, controls, and Aβ- dementia with Lewy bodies. However, this discriminative power could not be reproduced by applying pre-defined cut-offs. DISCUSSION: p-tau181 was the best single plasma marker for detecting AD at any stage. Specific cut-offs are needed to maximize diagnostic performances. HIGHLIGHTS: Phosphorylated tau (p-tau)181 provided a clear differentiation between controls and Alzheimer's disease (AD) participants, with evidence of increased levels in the preclinical stage of AD. Plasma biomarkers demonstrated that when amyloid co-pathology is removed from dementia with Lewy bodies (DLB), only glial fibrillary acidic protein and neurofilament light chain remain to predict DLB. Given the low prevalence of amyloid co-pathology in frontotemporal dementia (FTD), p-tau181 and its ratio with amyloid beta 42 are strong biomarkers to differentiate FTD from AD.

• MeSH
• Alzheimerova nemoc * krev   diagnóza   MeSH
• amyloidní beta-protein * krev   MeSH
• biologické markery krev   MeSH
• demence * krev   diagnóza   MeSH
• fosforylace MeSH
• gliový fibrilární kyselý protein * krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurofilamentové proteiny * krev   MeSH
• peptidové fragmenty * krev   MeSH
• proteiny tau * krev   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

INTRODUCTION: Chitinase-3-like protein 1 (CHI3L1) is a glycoprotein implicated in various neurological conditions. It is associated with neuroinflammation and tissue remodeling. The study aimed to validate the reference interval (RI) of serum (S) CHI3L1 in a control group, to correlate S CHI3L1 values with other biomarkers of neurodegenerative damage, and to estimate the diagnostic accuracy of S CHI3L1. METHODS: Samples from 108 healthy volunteers were used to estimate the S CHI3L1 RI. For the comparison, we used cerebrospinal fluid (CSF) and serum (S) samples from 121 patients with cognitive disorders, and cognitive deterioration was assessed using the Mini-Mental State Examination (MMSE). ELISA assays were used to determine the S CHI3L1, CSF, and S neurofilament light chain (NfL) levels; CSF and plasma β-amyloid peptide42; CSF and plasma β-amyloid peptide40; CSF total tau protein; CSF phosphorylated tau protein; and CSF alpha-synuclein. RESULTS: The estimated RI of S CHI3L1 was 14.44 to 63.11 μg/L. The cut-off value of S CHI3L1 was 34.37 μg/L. ROC analysis showed that S CHI3L1 has 81.4% sensitivity and 76.9% specificity. We found a moderate Spearman's rank correlation coefficient between the S CHI3L1 and age (rS = 0.486; p < 0.001) and between S CHI3L1 and S NfL (rS = 0.489; p < 0.001) in all groups. The Kruskal-Wallis test showed a significant overall difference in S CHI3L1 among diagnostic groups (p = 0.013). S CHI3L1 and CSF NfL had statistically significant effects on MMSE values (multiple R2 was 0.431). CONCLUSIONS: Our results suggest that S CHI3L1 reflects the severity of cognitive deficits assessed by MMSE. It can be used as a supportive biomarker in neurodegenerative diseases.

• MeSH
• alfa-synuklein mozkomíšní mok   krev   MeSH
• amyloidní beta-protein krev   mozkomíšní mok   MeSH
• biologické markery krev   mozkomíšní mok   MeSH
• dospělí MeSH
• kognitivní dysfunkce * krev   mozkomíšní mok   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurofilamentové proteiny mozkomíšní mok   krev   MeSH
• pohybové poruchy * krev   mozkomíšní mok   diagnóza   MeSH
• protein CHI3L1 * krev   mozkomíšní mok   MeSH
• proteiny tau mozkomíšní mok   krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Developmental remodeling shapes neural circuits via activity-dependent pruning of synapses and axons. Regulation of the cytoskeleton is critical for this process, as microtubule loss via enzymatic severing is an early step of pruning across many circuits and species. However, how microtubule-severing enzymes, such as spastin, are activated in specific neuronal compartments remains unknown. Here, we reveal that polyglutamylation, a post-translational tubulin modification enriched in neurons, plays an instructive role in developmental remodeling by tagging microtubules for severing. Motor neuron-specific gene deletion of enzymes that add or remove tubulin polyglutamylation-TTLL glutamylases vs. CCP deglutamylases-accelerates or delays neuromuscular synapse remodeling in a neurotransmission-dependent manner. This mechanism is not specific to peripheral synapses but also operates in central circuits, e.g., the hippocampus. Thus, tubulin polyglutamylation acts as a cytoskeletal rheostat of remodeling that shapes neuronal morphology and connectivity.

• MeSH
• hipokampus metabolismus   cytologie   MeSH
• kyselina polyglutamová * metabolismus   MeSH
• mikrotubuly * metabolismus   MeSH
• motorické neurony * metabolismus   MeSH
• myši MeSH
• nervosvalové spojení metabolismus   MeSH
• nervový přenos MeSH
• neurony * metabolismus   MeSH
• neuroplasticita * fyziologie   MeSH
• peptidsynthasy metabolismus   genetika   MeSH
• posttranslační úpravy proteinů MeSH
• spastin metabolismus   MeSH
• synapse metabolismus   MeSH
• tubulin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Spatial navigation deficits are early symptoms of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for AD. This study investigated effects of APOE genotype on spatial navigation in biomarker-defined individuals with amnestic mild cognitive impairment (aMCI) and associations of AD biomarkers and atrophy of AD-related brain regions with spatial navigation. METHODS: 107 participants, cognitively normal older adults (CN, n = 48) and aMCI individuals stratified into AD aMCI (n = 28) and non-AD aMCI (n = 31) groups, underwent cognitive assessment, brain MRI, and spatial navigation assessment using the Virtual Supermarket Test with egocentric and allocentric tasks and a self-report questionnaire. Cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, phosphorylated tau181 and total tau) and amyloid PET imaging were assessed in aMCI participants. RESULTS: AD aMCI participants had the highest prevalence of APOE ε4 carriers and worst allocentric navigation. CSF levels of AD biomarkers and atrophy in AD-related brain regions were associated with worse allocentric navigation. Between-group differences in spatial navigation and associations with AD biomarkers and regional brain atrophy were not influenced by APOE genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance. CONCLUSIONS: These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of APOE genotype. This highlights the role of AD pathology as measured by biomarkers, rather than genetic status, as a major factor in navigational impairment in aMCI, and emphasizes the assessment of spatial navigation as a valuable tool for early detection of AD.

• MeSH
• Alzheimerova nemoc * genetika   mozkomíšní mok   diagnostické zobrazování   komplikace   patofyziologie   patologie   MeSH
• amyloidní beta-protein mozkomíšní mok   MeSH
• apolipoprotein E4 * genetika   MeSH
• apolipoproteiny E * genetika   MeSH
• atrofie MeSH
• biologické markery mozkomíšní mok   MeSH
• genotyp MeSH
• kognitivní dysfunkce * genetika   mozkomíšní mok   diagnostické zobrazování   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   diagnostické zobrazování   MeSH
• neuropsychologické testy MeSH
• peptidové fragmenty mozkomíšní mok   MeSH
• pozitronová emisní tomografie MeSH
• prostorová navigace * fyziologie   MeSH
• proteiny tau mozkomíšní mok   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The neurotoxicity of phosphorylated tau protein (P-tau) and mitochondrial dysfunction play a significant role in the pathophysiology of Alzheimer's disease (AD). In vitro studies of the effects of P-tau oligomers on mitochondrial bioenergetics and reactive oxygen species production will allow us to evaluate the direct influence of P-tau on mitochondrial function. We measured the in vitro effect of P-tau oligomers on oxygen consumption and hydrogen peroxide production in isolated brain mitochondria. An appropriate combination of specific substrates and inhibitors of the phosphorylation pathway enabled the measurement and functional analysis of the effect of P-tau on mitochondrial respiration in defined coupling control states achieved in complex I-, II-, and I&II-linked electron transfer pathways. At submicromolar P-tau concentrations, we found no significant effect of P-tau on either mitochondrial respiration or hydrogen peroxide production in different respiratory states. The titration of P-tau showed a nonsignificant dose-dependent decrease in hydrogen peroxide production for complex I- and I&II-linked pathways. An insignificant in vitro effect of P-tau oligomers on both mitochondrial respiration and hydrogen peroxide production indicates that P-tau-induced mitochondrial dysfunction in AD is not due to direct effects of P-tau on the efficiency of the electron transport chain and on the production of reactive oxygen species.

• MeSH
• buněčné dýchání MeSH
• fosforylace MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• mitochondrie * metabolismus   MeSH
• mozek metabolismus   MeSH
• peroxid vodíku * metabolismus   MeSH
• proteiny tau * metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• spotřeba kyslíku MeSH
• transport elektronů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BackgroundKLOTHO-VS heterozygosity (KL-VSHET) and soluble α-Klotho (sαKl) protein interfere with Alzheimer's disease (AD) pathophysiology, but the specific relationships remain unclear. This study explored these associations across the AD continuum, focusing on core AD biomarkers and markers of neurodegeneration, neuroinflammation, and synaptic dysfunction.ObjectiveWe investigated whether 1) KL-VSHET is associated with lower AD biomarker burden (Aβ42, Aβ42/40 ratio, P-tau181, T-tau) and neurodegeneration (NfL); 2) sαKl relates to AD biomarkers, neurodegeneration (NfL), neuroinflammation (GFAP), and synaptic dysfunction (Ng); 3) associations vary by APOE ε4 status and clinical subgroup.MethodsParticipants (n = 223) were categorized as cognitively healthy (n = 38), aMCI-AD (n = 94), and AD dementia (n = 91). KLOTHO genotyping was available for 128 participants; 138 had cerebrospinal fluid (CSF) and serum sαKl measurements; and 42 had both. Multiple linear regression evaluated associations between KL-VSHET, sαKl levels, and biomarkers, stratified by APOE ε4 status and clinical subgroup.ResultsOverall, the associations between KL-VSHET and higher CSF Aβ42 and Aβ42/40 ratio were non-significant (ps ≥ 0.059) except when restricted to APOE ε4 carriers only (β = 0.11, p = 0.008 and β = 0.16, p = 0.033, respectively). Within clinical subgroups, KL-VSHET was positively associated with Aβ42/40 ratio only in aMCI-AD (β = 0.23, p = 0.034). No significant associations were observed between KL-VSHET and tau biomarkers or NfL. For sαKl, associations with biomarkers were non-significant except for a negative association of serum sαKl with P-tau181 in aMCI-AD (β = -0.25, p = 0.036) and a positive association with Aβ42/40 ratio in APOE ε4 non-carriers (β = 0.24 p = 0.047).ConclusionsKL-VSHET may help protect against amyloid pathology, particularly in the presence of APOE ε4, and regardless of APOE status in aMCI-AD.

• MeSH
• Alzheimerova nemoc * mozkomíšní mok   genetika   MeSH
• amyloidní beta-protein mozkomíšní mok   MeSH
• apolipoprotein E4 genetika   MeSH
• biologické markery mozkomíšní mok   MeSH
• glukuronidasa * genetika   MeSH
• heterozygot MeSH
• kognitivní dysfunkce mozkomíšní mok   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• peptidové fragmenty mozkomíšní mok   MeSH
• proteiny Klotho genetika   MeSH
• proteiny tau mozkomíšní mok   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The disease currently known as frontotemporal dementia (FTD) has undergone a complex evolution from its first description by Arnold Pick and later by Alois Alzheimer, through the first clinicopathological criteria introduced by David Neary and David Mann, to its current nomenclatural perception as a complex clinicopathological entity. Currently, Frontotemporal lobar degeneration is viewed as a heterogeneous syndrome caused by progressive degeneration of the frontal and temporal lobes of the brain. Clinically, it can manifest as three syndromes of frontotemporal dementia (behavioral variant of FTD, progressive non-fluent aphasia and semantic dementia) but also as so-called "overlap" syndromes involving corticobasal degeneration and progressive supranuclear palsy. Its prevalence is about 10 % among all dementias and 40 % among dementias with onset between 45 and 65 years of age. The clinical manifestation of the different subtypes varies, the common denominator being behavioral disturbances and impairment of fatic, gnostic and executive functions. Mnestic and visuo-spatial functions, although preserved for a relatively long time, are superimposed by personality disintegration, fatic, gnostic and executive dysfunction. Compared with Alzheimer's disease, it generally has an earlier age of onset, a more rapid course and more devastating impairment of individual cognitive domains. FTD has a heritability of more than 30 % according to current knowledge. The main genes involved are MAPT, C9orf72 and GRN. More rarely affected genes are VCP, TDP-43, FUS and CHMP2B. In our article, we focus on the genetics of FTD and the clinic-genetic-pathological correlations. We also aim to provide a plastic picture of how individual mutations affect the molecular mechanisms of neurodegeneration.

• MeSH
• epigeneze genetická genetika   MeSH
• frontotemporální demence * diagnóza   genetika   klasifikace   MeSH
• genetické testování metody   MeSH
• lidé MeSH
• primární progresivní nonfluentní afázie diagnóza   genetika   MeSH
• progranuliny genetika   MeSH
• proteiny tau genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Intracellular trafficking involves an intricate machinery of motor complexes, including the dynein complex, to shuttle cargo for autophagolysosomal degradation. Deficiency in dynein axonemal chains, as well as cytoplasmic light and intermediate chains, have been linked with ciliary dyskinesia and skeletal dysplasia. The cytoplasmic dynein 1 heavy chain protein (DYNC1H1) serves as a core complex for retrograde trafficking in neuronal axons. Dominant pathogenic variants in DYNC1H1 have been previously implicated in peripheral neuromuscular disorders (NMD) and neurodevelopmental disorders (NDD). As heavy-chain dynein is ubiquitously expressed, the apparent selectivity of heavy chain dyneinopathy for motor neuronal phenotypes remains currently unaccounted for. Here, we aimed to evaluate the full DYNC1H1-related clinical, molecular and imaging spectrum, including multisystem features and novel phenotypes presenting throughout life. We identified 47 cases from 43 families with pathogenic heterozygous variants in DYNC1H1 (aged 0-59 years) and collected phenotypic data via a comprehensive standardized survey and clinical follow-up appointments. Most patients presented with divergent and previously unrecognized neurological and multisystem features, leading to significant delays in genetic testing and establishing the correct diagnosis. Neurological phenotypes include novel autonomic features, previously rarely described behavioral disorders, movement disorders and periventricular lesions. Sensory neuropathy was identified in nine patients (median age of onset 10.6 years), of which five were only diagnosed after the second decade of life, and three had a progressive age-dependent sensory neuropathy. Novel multisystem features included primary immunodeficiency, bilateral sensorineural hearing loss, organ anomalies and skeletal manifestations, resembling the phenotypic spectrum of other dyneinopathies. We also identified an age-dependent biphasic disease course with developmental regression in the first decade and, following a period of stability, neurodegenerative progression after the second decade of life. Of note, we observed several cases in whom neurodegeneration appeared to be prompted by intercurrent systemic infections with double-stranded DNA viruses (Herpesviridae) or single-stranded RNA viruses (Ross River fever, SARS-CoV-2). Moreover, the disease course appeared to be exacerbated by viral infections regardless of age and/or severity of neurodevelopmental disorder manifestations, indicating a role of dynein in anti-viral immunity and neuronal health. In summary, our findings expand the clinical, imaging and molecular spectrum of pathogenic DYNC1H1 variants beyond motor neuropathy disorders and suggest a life-long continuum and age-related progression due to deficient intracellular trafficking. This study will facilitate early diagnosis and improve counselling and health surveillance of affected patients.

• MeSH
• cytoplazmatické dyneiny * genetika   MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• neurovývojové poruchy genetika   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The spread of tau pathology closely correlates with the disease course and cognitive decline in Alzheimer's disease (AD). Tau-targeting immunotherapies are being developed to stop the spread of tau pathology and thus halt disease progression. In this post hoc analysis of the ADAMANT clinical trial, we examined the performance of AADvac1, an active immunotherapy targeting the microtubule-binding region (MTBR) of tau, in a subgroup of participants with elevated plasma p-tau217, indicating AD-related neuropathological changes. METHODS: ADAMANT was a 24-month, randomized, placebo-controlled, parallel-group, double-blinded, multicenter, phase 2 clinical trial in subjects with mild AD. The trial participants were randomized 3:2 to receive six doses of AADvac1 or placebo at 4-week intervals, followed by five booster doses at 14-week intervals. The primary outcome was safety. The secondary outcomes were the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Alzheimer's Disease Cooperative Study - Activities of Daily Living score for Mild Cognitive Impairment 18-item version (ADCS-ADL-MCI-18), and immunogenicity. Volumetric MRI, plasma neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were exploratory outcomes. The inclusion criterion for this post-hoc analysis was a baseline plasma p-tau217 level above the cutoff for AD. RESULTS: Among 196 ADAMANT participants, 137 were positive for plasma p-tau217 (mean age 71.4 years, 59% women). AADvac1 was safe and well tolerated in this subgroup. AADvac1 reduced the rate of accumulation of log-plasma NfL by 56% and that of GFAP by 73%. The treatment differences in the CDR-SB and ADCS-ADL-MCI-18 scores favored AADvac1 but were not statistically significant. AADvac1 had no effect on whole-brain volume but nonsignificantly reduced the loss of brain cortical tissue in several regions. Importantly, the impact on the study outcomes was more pronounced in participants with higher anti-tau antibody levels. CONCLUSIONS: These results suggest that AADvac1 tau immunotherapy can reduce plasma biomarkers of neurodegeneration and neuroinflammation. These findings and possible observations on brain atrophy and cognition are hypothesis-generating and warrant further evaluation in a larger clinical trial. TRIAL REGISTRATION: EudraCT 2015-000630-30 (primary) and NCT02579252.

• MeSH
• aktivní imunoterapie metody   MeSH
• Alzheimerova nemoc * krev   terapie   imunologie   MeSH
• biologické markery krev   MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• proteiny tau * krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• testy pro posouzení mentálních funkcí a demence MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH