The DOI matches its Crossref record; 52 of the 53 references it cites were found in a registry or an index; none of the 26 sources its claims cite is checked for support yet.
Decreased cerebrospinal fluid Aβ 42 correlates with brain atrophy in cognitively normal elderly
Open accessAbstract
Objective: For therapies for Alzheimer's disease (AD) to have the greatest impact, it will likely be necessary to treat individuals in the “preclinical” (presymptomatic) stage. Fluid and neuroimaging measures are being explored as possible biomarkers of AD pathology that could aid in identifying individuals in this stage to target them for clinical trials and to direct and monitor therapy. The objective of this study was to determine whether cerebrospinal fluid (CSF) biomarkers for AD suggest the presence of brain damage in the preclinical stage of AD. Methods: We investigated the relation between structural neuroimaging measures (whole‐brain volume) and levels of CSF amyloid‐β (Aβ) 40 , Aβ 42 , tau, and phosphorylated tau 181 (ptau 181 ), and plasma Aβ 40 and Aβ 42 in well‐characterized research subjects with very mild and mild dementia of the Alzheimer type (n = 29) and age‐matched, cognitively normal control subjects (n = 69). Results: Levels of CSF tau and ptau 181 , but not Aβ 42 , correlated inversely with whole‐brain volume in very mild and mild dementia of the Alzheimer type, whereas levels of CSF Aβ 42 , but not tau or ptau 181 , were positively correlated with whole‐brain volume in nondemented control subjects. Interpretation: Reduction in CSF Aβ 42 , likely reflecting Aβ aggregation in the brain, is associated with brain atrophy in the preclinical phase of AD. This suggests that there is toxicity associated with Aβ aggregation before the onset of clinically detectable disease. Increases in CSF tau (and ptau 181 ) are later events that correlate with further structural damage and occur with clinical onset and progression. Ann Neurol 2009;65:176–183
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TL;DR
In cognitively normal elderly, lower CSF Aβ42 was associated with smaller whole-brain volume, suggesting Aβ-related brain atrophy in the preclinical stage of Alzheimer’s disease. In very mild/mild dementia of the Alzheimer type, CSF tau and ptau181—but not Aβ42—correlated inversely with whole-brain volume.
Key findings
- Among non-demented controls (CDR 0, n=69), CSF Aβ42 was positively correlated with whole-brain volume, whereas CSF Aβ40, tau, ptau181, and plasma Aβ40/Aβ42 were not.
- Non-demented individuals with CSF Aβ42 <500 pg/mL had significantly smaller whole-brain volumes than those with CSF Aβ42 ≥500 pg/mL (p=0.0005); hippocampal volume was also smaller (mean=6793.59, SD=786.46, n=26 vs mean=7338.48, SD=720.09, n=32; p=0.008).
- In the PET PIB subset (n=37), all PIB-positive individuals had CSF Aβ42 <500 pg/mL (13/13, 100% sensitivity), and most PIB-negative individuals had CSF Aβ42 ≥500 pg/mL (20/24, 83% specificity).
- In very mild/mild DAT (CDR>0, n=29), whole-brain volume was inversely correlated with CSF tau and ptau181, but not with CSF Aβ42, CSF Aβ40, or plasma Aβ40/Aβ42.
Methods
- Community-dwelling volunteers (n=98; ages 60–91) from the Washington University ADRC: CDR 0 n=69, CDR 0.5 n=21, CDR 1 n=8; CDR 0.5 and CDR 1 were combined as CDR>0 (n=29).
- CSF and plasma Aβ40, Aβ42, tau, and ptau181 were measured by ELISA; MRI-derived normalized whole-brain volume and hippocampal volume were obtained, with PET PIB amyloid imaging in 37 participants.
- Analyses used t-tests/chi-square for group comparisons and bivariate or age-adjusted partial Pearson correlations between imaging and fluid measures, with p=0.05 and no correction for multiple comparisons.
Limitations
- Stated: no correction for multiple comparisons was applied, so some significant differences may be due to chance; the CDR 1 group was too small (n=8) for meaningful separate analysis.
- Stated: hippocampal volumes were unavailable for 12 of 98 subjects due to Freesurfer processing errors.
- Evident: the design is cross-sectional, with LP/blood and MRI performed within 2 years of each other, so temporal or causal direction cannot be established from these correlations.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“levels of CSF Aβ42, but not tau or ptau181, was positively correlated with whole brain volume in non-demented controls.”
- Also stated in: § Results · plain
“nWBV was significantly correlated with CSF Aβ42 (Fig. 1B); non-demented individuals with low CSF Aβ42 had smaller brain volumes than those with higher CSF Aβ42.”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Abstract > Results:
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“brain volume was not associated with levels of CSF Aβ40 (Fig. 1A)”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean hippocampal volume was also smaller in CDR 0 subjects with CSF Aβ42 <500 pg/mL (mean=6793.59, SD=786.46, n=26) compared to those with CSF Aβ42 values ≥500 pg/mL (mean=7338.48, SD=720.09, n=32) (p=0.008).”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“nor with plasma Aβ40 (r=−0.0390, p=0.776)”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ptau181 (r=−0.0020, p=0.987)”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Non-demented individuals with CSF Aβ42 <500 pg/mL (likely indicative of brain amyloid) exhibited significantly smaller brain volumes (p=0.0005) on average than those with CSF Aβ42 ≥500 pg/mL (Fig. 1F).”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“tau (Fig. 1C)”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of CSF tau and ptau181, but not Aβ42, correlated inversely with whole brain volume in very mild/mild DAT”
- Also stated in: § Results · plain
“whole brain volume was inversely correlated with levels of CSF tau (Fig. 2C)”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Abstract > Results:
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“None of the fluid measures correlated with hippocampal volume in the very mildly/mildly demented cohort (Table 2).”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Subjects with very mild/mild DAT also exhibited the typical AD fluid biomarker phenotype characterized by significantly lower mean levels of CSF Aβ42, higher CSF tau, ptau181 and the tau(s)/Aβ42 ratios, 8-11, 13, 14 with no change in mean levels of CSF Aβ40 or plasma Aβ40 or Aβ42.”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
Strength:plain· not yet calibratedn = 29Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 12
- Probably not a substantial claim. 11
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“with no change in mean levels of CSF Aβ40 or plasma Aβ40 or Aβ42.”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
Strength:plain· not yet calibratedn = 29Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“AD pathology is estimated to begin a decade or longer prior to the appearance of any cognitive symptoms and signs of dementia (a stage termed “preclinical AD”), with impairments becoming clinically detectable only after substantial neuronal cell death has taken place.1-5”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Introduction
What the sources say
- Not checked yetcites [1] Price J Ko A Wade M Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer's disease Arch Neurol 2001 58 1395 1402 11559310 source
- Not checked yetcites [2] Gomez-Isla T Price JL McKeel DW Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease J Neurosci 1996 16 4491 4500 8699259 PMC6578866 source
- Not checked yetcites [3] Morris J Price J Pathologic correlates of nondemented aging, mild cognitive impairment, and early stage Alzheimer's disease J Mol Neurosci 2001 17 101 118 11816784
- Not checked yetcites [4] Hulette CM Welsh-Bohmer KA Murray MG Neuropathological and neuropsychological changes in “normal” aging: Evidence for preclinical Alzheimer disease in cognitively normal individuals J Neuropathol Exp Neurol 1998 57 1168 1174 9862640 source
- Not checked yetcites [5] Markesbery W Schmitt F Kryscio R Neuropathologic substrate of Mild Cognitive Impairment Arch Neurol 2006 63 38 46 16401735 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Whole brain atrophy, the presumed consequence of years of axonal and neuronal degeneration, is a fundamental but not specific feature of AD and has been quantified antemortem by magnetic resonance imaging (MRI) in both cross-sectional and longitudinal studies. 6, 7”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Introduction
What the sources say
- Not checked yetcites [6] Kantarci K Jack CR Jr Quantitative magnetic resonance techniques as surrogate markers of Alzheimer's disease NeuroRx 2004 1 196 205 15717020 PMC534925
- Not checked yetcites [7] Scahill RI Fox NC Longitudinal imaging in dementia Br J Radiol 2007 80 Spec No 2 S92 98 18445749
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- The authors state this as an assumption: Whole brain atrophy is the consequence of years of axonal and neuronal degeneration.
None of the sources cited for this claim have been checked yet.
In the paper
“Levels of CSF Aβ42 are typically reduced in dementia of the Alzheimer type (DAT),8-11 reflecting its aggregation and deposition as amyloid in the brain,12”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Introduction
What the sources say
- Not checked yetcites [8] Sunderland T Linker G Mirza N Decreased β-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer's disease JAMA 2003 289 2094 2103 12709467 source
- Not checked yetcites [9] Galasko D Chang L Motter R High cerebrospinal fluid tau and low amyloid β42 levels in the clinical diagnosis of Alzheimer's disease and relation to apolipoprotein E genotype Arch. Neurol 1998 55 937 945 9678311 source
- Not checked yetcites [10] Kanai M Matsubara E Isoe K Longitudinal study of cerebrospinal fluid levels of tau, Aβ1-40, and Aβ1-42(43) in Alzheimer's disease: A study in Japan Ann. Neurol 1998 44 17 26 9667589 source
- Not checked yetcites [11] Motter R Vigo-Pelfrey C Kholodenko D Reduction of β-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease Ann. Neurol 1995 38 643 648 7574461 source
- Not checked yetcites [12] Fagan A Mintun M Mach R Inverse relation between in vivo amyloid imaging load and CSF Aβ42 in humans Ann Neurol 2006 59 512 519 16372280 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“levels of CSF tau and phosphorylated tau (ptau) species are elevated in DAT8, 13, 14 and are hypothesized to reflect the presence of neurofibrillary tangles and/or neurodegeneration,15, 16 although not all studies support this conclusion.17”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Introduction
What the sources say
- Not checked yetcites [8] Sunderland T Linker G Mirza N Decreased β-amyloid1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer's disease JAMA 2003 289 2094 2103 12709467
- Not checked yetcites [13] Andreasen N Vanmechelen E Van de Voorde A Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease: A community based follow up study J. Neurol. Neurosurg. Psych 1998 64 298 305 PMC2170016 9527138
- Not checked yetcites [14] Arai H Terajima M Miura M Tau in cerebrospinal fluid: A potential diagnostic marker in Alzheimer's disease Ann. Neurol 1995 38 649 652 7574462
- Not checked yetcites [15] Tapiola T Overmyer M Lehtovirta M The level of cerebrospinal fluid tau correlates with neurofibrillary tangles in Alzheimer's disease Neuroreport 1997 8 3961 3963 9462474
- Not checked yetcites [16] Buerger K Ewers M Pirttila T CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease Brain 2006 129 3035 3041 17012293 source
- Not checked yetcites [17] Engelborghs S Sleegers K Cras P No association of CSF biomarkers with APOEepsilon4, plaque and tangle burden in definite Alzheimer's disease Brain 2007 130 2320 2326 17586559
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The rate of postmortem confirmation of AD clinical diagnosis in our Center is 92% 22, including the very mild CDR 0.5 stage.”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Subjects and Methods > Subjects
What the sources say
- Not checked yetcites [22] Storandt M Grant E Miller J Morris J Longitudinal course and neuropathologic outcomes in original vs revised MCI and in pre-MCI Neurology 2006 67 467 473 16894109
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“As chronological age was associated with fluid and imaging measures, correlations were adjusted for age in all analyses.”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“without correction for multiple comparisons. Since the Type I error rate rises with increasing numbers of statistical tests, some statistically significant differences reported may be due to chance.”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Subjects and Methods > Statistical Analyses
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the CSF tau/Aβ42 ratio predicts future cognitive decline in cognitively normal elders 34, 50 and individuals with MCI,51”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Discussion
What the sources say
- Not checked yetcites [34] Fagan A Roe C Xiong C Cerebrospinal fluid tau/Aβ42 ratio as a prediction of cognitive decline in nondemented older adults Arch. Neurol 2007 64 343 349 17210801 source
- Not checked yetcites [50] Li G Sokal I Quinn J CSF tau/Aβ42 ratio for increased risk of mild cognitive impairment: A follow-up study Neurology 2007 69 631 639 17698783
- Not checked yetcites [51] Hansson O Zetterberg H Buchhave P Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: A follow-up study Lancet Neurol 2006 5 228 234 16488378
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The groups differed significantly with regard to age (slightly older in the CDR>0 group), education (less in the CDR>0 group), and MMSE scores (lower in the CDR>0 group).”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Reductions in CSF Aβ42 reflect the presence of amyloid plaques but perhaps also diffuse (non-fibrillar) plaques and/or concomitant Aβ oligomer formation, both of which could contribute to neurotoxicity (neuritic and/or cellular) and consequent volume loss, but would not be visualized with PET PIB.”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“has been reported to generate volumes with a high correspondence to manually generated volumes. 31”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Subjects and Methods > Magnetic Resonance Imaging Acquisition and Image Processing
What the sources say
- Not checked yetcites [31] Fischl B Salat D Busa E Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain Neuron 2002 33 341 355 11832223 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Mahalanobis Distance and Cook's Distance methods 33 were used to define multivariate outliers, and partial correlations (controlling for age) were again performed on the new data set in which outliers were omitted.”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Subjects and Methods > Statistical Analyses
What the sources say
- Not checked yetcites [33] Cohen J Cohen P West S Aiken L Applied Multiple Regression/Correlations Analysis for the Behavioral Sciences 2003 Lawrence Erlbaum Associates Mahwah, New Jersey Third Edition
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Increases in CSF tau (and ptau181) are later events that correlate with further structural damage and occur with clinical onset and progression.”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Abstract > Interpretation:
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“LP/blood collection and MRI were performed within 2 years of each other.”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Subjects and Methods > Subjects
Strength:plain· not yet calibratedn = 98Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“CSF samples were free from any blood contamination.”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Subjects and Methods > CSF and Plasma Collection, Processing, and Biomarker Measurement
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Hippocampal volumes were obtained from all but 12 of the 98 subjects (omissions due to Freesurfer processing errors).”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Subjects and Methods > Magnetic Resonance Imaging Acquisition and Image Processing
Strength:plain· not yet calibratedn = 98Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The authors state this as an assumption.
Whole brain atrophy is the consequence of years of axonal and neuronal degeneration.
“Whole brain atrophy, the presumed consequence of years of axonal and neuronal degeneration, is a fundamental but not specific feature of AD”
The paper relies on this without support.
The relationship between fluid measures and brain volumetric measures is unclear, especially in non-demented elderly individuals and those with early stage DAT.
“The extent to which these fluid measures relate to brain volumetric measures remains unclear, especially in non-demented elderly individuals and those with early stage DAT.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“low concentrations of Aβ42 in the cerebrospinal fluid (CSF) reflect the presence of cerebral Aβ deposition, likely as a result of Aβ42 being sequestered into amyloid plaques, changing the equilibrium between the brain and CSF pools of Aβ (20-22).”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [22]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Given that a CSF Aβ42 concentration lower than 500 pg/mL has been utilized as a reliable threshold for the presence of cerebral Aβ deposition in humans (7, 19, 22, 26)”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [22]
In the citing paper
“That the best predictor for conversion to MCI and then AD is a decrease in the levels of extracellular Aβ42 might have seemed surprising to proponents of the prevalent extracellular Aβ cascade hypothesis.”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [48]
In the citing paper
“Recently it is becoming apparent that the earliest diagnostic change indicating that an individual without known cognitive deficits will go on to decline cognitively and develop AD is a drop in levels of Aβ42 in the CSF [15, 48].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [48]
Citations
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“, binding to plasma proteins), variable efflux of CSF Ab to plasma is likely related to cerebral plaque Ab(27,28) with a reduction in CSF Ab indicating increased cortical amyloid deposition.(24,29) Vascular Ab deposits of CAA consist mainly of Ab1–40 while cerebral amyloid plaques are primarily composed of Ab1–42.”
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“, 2007), or reduced cerebrospinal fluid (CSF) Aβ levels, is associated with brain atrophy in CU participants (Becker et al., 2011; Fagan et al., 2009; Fjell et al., 2010a; Mormino et al., 2009; Schott et al., 2010; Storandt et al., 2009; Tosun et al., 2010).”
BackgroundMAPT R406W increases tau T217 phosphorylation in absence of amyloid pathology
Sato, C., Mallipeddi, N., Ghoshal, N., Wright, B. A., Day, G. S., Davis, A. A., Kim, A. H., Zipfel, G. J., Bateman, R. J., Gabelle, A., et al. (2021) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51435 · Cited by 21
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Neuropathology‐based APOE genetic risk score better quantifies Alzheimer's risk
Deming, Y. K., Vasiljevic, E., Morrow, A. R., Miao, J., Hulle, C. V., Jonaitis, E. M., Ma, Y., Whitenack, V. M., Kollmorgen, G., Wild, N., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.12990 · Cited by 22
“The robust prototype β-Amyloid(1-40) CSF immunoassay is for investigational use only and not commercially available.”
BackgroundMethodLecanemab: A Humanized Monoclonal Antibody for the Treatment of Early Alzheimer Disease
Park, J., Simpson, C., & Patel, K. (2023) · Annals of Pharmacotherapy · doi:10.1177/10600280231218253 · Cited by 25
Zetterberg, H., Lautner, R., Skillbäck, T. B., Rosén, C., Shahim, P., Mattsson, N., & Blennow, K. (2014) · Advances in clinical chemistry · doi:10.1016/b978-0-12-800141-7.00005-x · Cited by 21
Association of plasma β-amyloid with MRI markers of structural brain aging the 3-City Dijon study
Kaffashian, S., Tzourio, C., Soumaré, A., Dufouil, C., Mazoyer, B. M., Schraen‐Maschke, S., Buée, L., & Debette, S. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.03.016 · Cited by 25
Genetic variation modifies risk for neurodegeneration based on biomarker status
Hohman, T. J., Koran, M. E. I., & Thornton‐Wells, T. A. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00183 · Cited by 22
“ORIGINAL RESEARCH ARTICLE published: 04 August 2014 doi: 10.3389/fnagi.2014.00183 Genetic variation modifies risk for neurodegeneration based on biomarker status”
BackgroundInfluentialRisk Classification in Mild Cognitive Impairment Patients for Developing Alzheimer's Disease
Zhou, B., Initiative, T. A. D. N., Nakatani, E., Teramukai, S., Nagai, Y., & Fukushima, M. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-112117 · Cited by 22
“The CSF protein A 42 and tau or MRI findings have been hypothesized to have potential utility in identifying patient populations that are most likely to benefit with the lowest risk of harm from new therapies [22–25].”
Translational proteomics in Alzheimer's disease and related disorders
Ghidoni, R., Paterlini, A., & Benussi, L. (2012) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2012.10.012 · Cited by 22
Hayes, J. P., Moody, J. N., Roca, J. G., & Hayes, S. M. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.102156 · Cited by 21
“The lack of interaction between BMI and polygenic risk for AD on CSF biomarkers was surprising, as there is evidence that atrophy reflects the accumulation of Aβ, tau, and p-tau in the brain (Fagan et al., 2009; Jack et al., 2013).”
BackgroundLin, P., Chen, W., Yuan, F., Sheng, L., Wu, Y., Zhang, W., Li, G., Xu, H., & Li, X. (2017) · Journal of Chromatography B · doi:10.1016/j.jchromb.2017.10.047 · Cited by 21
Genetic modification of the relationship between phosphorylated tau and neurodegeneration
Hohman, T. J., Koran, M. E. I., Thornton‐Wells, T. A., & Initiative, A. D. N. (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.12.022 · Cited by 21
The Entorhinal Cortex Atrophy Score Is Diagnostic and Prognostic in Mild Cognitive Impairment
Traschütz, A., Enkirch, S. J., Polomac, N., Widmann, C. N., Schild, H. H., Heneka, M. T., & Hattingen, E. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-181150 · Cited by 20
Upregulation of Aβ42 in the Brain and Bodily Fluids of Rhesus Monkeys with Aging
Zhao, Q., Lü, J., Yao, Z., Wang, S., Zhu, L., Wang, J., & Chen, B. (2016) · Journal of Molecular Neuroscience · doi:10.1007/s12031-016-0840-6 · Cited by 20
“Although these results agree with those of the brain (see previous discussion), they do not agree with those of Fagan et al. (2009) who reported that brain atrophy in humans associates with a decreased Aβ42 level in the CSF.”
ResultKämäläinen, A., Herukka, S., Hartikainen, P. H., Helisalmi, S., Moilanen, V., Knuuttila, A., Jansson, L., Tienari, P. J., & Remes, A. M. (2015) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000371704 · Cited by 19
Solé‐Padullés, C., Lladó, A., Bartrés‐Faz, D., Fortea, J., Sánchez‐Valle, R., Bosch, B., Antonell, A., Molinuevo, J. L., & Rami, L. (2011) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2010.12.001 · Cited by 19
Molecular Neuroimaging in Alzheimer's Disease
Matsuda, H., & Imabayashi, E. (2011) · Neuroimaging Clinics of North America · doi:10.1016/j.nic.2011.11.005 · Cited by 21
Franco, R., Navarro, G., & Martínez‐Pinilla, E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133297 · Cited by 17
Soldan, A., Pettigrew, C. A., Moghekar, A., & Albert, M. (2016) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617716000722 · Cited by 18
“Low or declining levels of CSF Aβ1-42 among cognitively normal subjects have also been linked to greater atrophy rates, particularly in frontal-parietal regions (Fagan et al., 2009; Mattsson, Insel, Nosheny, Tosun, et al., 2014) and reduced cortical thickness (Tosun, Schuff, Shaw, Trojanowski, & Weiner, 2011).”
BackgroundJargiło, A., Grabowska, I., Radecka, H., Sulima, M., Marszałek, I., Wysłouch‐Cieszyńska, A., Dehaen, W., & Radecki, J. (2013) · Electroanalysis · doi:10.1002/elan.201200537 · Cited by 17
Critical Comparison of Different Biomarkers for Alzheimer’s Disease in a Clinical Setting
Weise, D., Tiepolt, S., Awissus, C., Hoffmann, K., Lobsien, D., Kaiser, T., Barthel, H., Sabri, O., & Gertz, H. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150229 · Cited by 18
Koops, E. A., Dutta, J., Hanseeuw, B. J., Becker, J. A., Egroo, M. V., Prokopiou, P. C., Price, J. C., Arnold, S. E., Sperling, R. A., Johnson, K. A., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14385 · Cited by 16
Monoclonal antibody therapy for Alzheimer's disease focusing on intracerebral targets
Gu, X., Long, Q., Qi, Q., Zhou, J., Chen, S., & Wang, L. (2024) · BioScience Trends · doi:10.5582/bst.2023.01288 · Cited by 17
Li, L., Ma, Y., Bi, Y., Sun, F.-R., Hu, H., Hou, X., Xu, W., Shen, X., Dong, Q., Tan, L., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201192 · Cited by 17
Barthélemy, N. R., Bateman, R. J., Marin, P., Bécher, F., Sato, C., Lehmann, S., & Gabelle, A. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/226977 · Cited by 16
TOMM40 poly-T Variants and Cerebrospinal Fluid Amyloid Beta Levels in the Elderly
Pomara, N., Bruno, D., Nierenberg, J. J., Sidtis, J. J., Martiniuk, F. T., Mehta, P. D., Zetterberg, H., & Blennow, K. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0459-5 · Cited by 15
A Window into the Heterogeneity of Human Cerebrospinal Fluid Aβ Peptides
Ghidoni, R., Paterlini, A., Albertini, V., Stoppani, E., Binetti, G. G., Fuxé, K., Benussi, L., & Agnati, L. F. (2011) · BioMed Research International · doi:10.1155/2011/697036 · Cited by 15
“Of note, Aβ1-42 is associated with impairment of cognitive function from a potentially early to a later disease phase [35–37].”
BackgroundBiomarkers for the clinical evaluation of the cognitively impaired elderly: amyloid is not enough
McEvoy, L. K., & Brewer, J. B. (2012) · Imaging in Medicine · doi:10.2217/iim.12.27 · Cited by 15
Hata, S., Taniguchi, M., Piao, Y., Ikeuchi, T., Fagan, A. M., Holtzman, D. M., Bateman, R. J., Sohrabi, H. R., Martins, R. N., Gandy, S., et al. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-16 · Cited by 15
Self-citationThe contributions of metabolomics in the discovery of new therapeutic targets in Alzheimer's disease
Samey, R. A., Antier, D., Mavel, S., Dufour‐Rainfray, D., Balageas, A., Beaufils, É., Emond, P., Foucault‐Fruchard, L., & Chalon, S. (2021) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12654 · Cited by 16
Biomarcadores en la enfermedad de Alzheimer
Ribas, G. G., López-Sendón, J. L., & Caldentey, J. G. (2014) · Revista de Neurología · doi:10.33588/rn.5807.2013394 · Cited by 14
Koric, L., Félician, O., & Ceccaldi, M. P. (2011) · Revue Neurologique · doi:10.1016/j.neurol.2010.10.007 · Cited by 19
Allison, S. L., Jonaitis, E. M., Koscik, R. L., Hermann, B. P., Mueller, K. D., Cary, R. P., Ma, Y., Rowley, H. A., Carlsson, C. M., Asthana, S., et al. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.01.030 · Cited by 15
Cerebrospinal Fluid Analysis Should Be Considered in Patients with Cognitive Problems
Zetterberg, H., Mattsson, N., & Blennow, K. (2010) · International Journal of Alzheimer s Disease · doi:10.4061/2010/163065 · Cited by 14
“This seems to be the earliest biochemical change during the course of AD [9–11].”
BackgroundUtility of spontaneous animal models of Alzheimer’s disease in preclinical efficacy studies
Zeiss, C. J. (2020) · Cell and Tissue Research · doi:10.1007/s00441-020-03198-6 · Cited by 16
Liu, X., Teng, Z., Cui, C., Wang, R., Liu, M., & Zhang, Y. (2014) · Journal of Molecular Neuroscience · doi:10.1007/s12031-013-0216-0 · Cited by 14
“However, based on the low levels of soluble Aβ present in the normal-aged brain (Fagan et al. 2009), there may exist a balance between Aβ production and clearance in the brain.”
Omachi, Y., Ito, K., Arima, K., Matsuda, H., Nakata, Y., Sakata, M., Sato, N., Nakagome, K., & Motohashi, N. (2015) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12326 · Cited by 13
“(11)C-PiB binds to insoluble (fibrillar) Aβ in compact or core plaques and cerebral amyloid angiopathy highly selectively, but may fail to bind to soluble (non-fibrillar) Aβ in diffuse plaques and Aβ oligomers.(10,11,38,39) Additional pathological evaluations are necessary to determine the diagnosis in PiB-negative pa…”
Robertson, E. L., Boehnke, S. E., Silva, N. M. L. E., Armitage‐Brown, B., Winterborn, A., Cook, D. J., Felice, F. G. D., & Munoz, D. P. (2022) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12289 · Cited by 13
Rogojin, A., Gorbet, D. J., Hawkins, K. M., & Sergio, L. E. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1054516 · Cited by 12
“Grey matter atrophy has been reported in cognitively healthy individuals positive for amyloid pathology (Fagan et al., 2009; Mormino et al., 2009; Villeneuve et al., 2014) and tau pathology (Wang et al.”
BackgroundRecent advances in pre-clinical diagnosis of Alzheimer’s disease
Zhou, J., Benoit, M., & Sharoar, M. G. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00733-4 · Cited by 14
“However, CSF Aβ42 levels can vary based upon differences in pre-analytical samples and storage, individual differences in amyloid levels between patients, and decreased brain volume (Fagan et al. 2009; Shaw et al. 2009; Shaw et al. 2011).”
BackgroundAn Exploratory Study of Cognitive Involvement in Hereditary Transthyretin Amyloidosis
Durmuş, H., Çakar, A., Demirci, H., Alaylıoğlu, M., Gezen‐Ak, D., Dursun, E., & Parman, Y. (2021) · Acta Neurologica Scandinavica · doi:10.1111/ane.13507 · Cited by 12
van Waalwijk van Doorn, L. J. C., Gispert, J. D., Kuiperij, H. B., Claassen, J. A. H. R., Arighi, A., Baldeiras, I., Blennow, K., Bozzali, M., Castelo-Branco, M., Cavedo, E., et al. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160668 · Cited by 13
“Indeed, it has been suggested that CSF A (cid:2) 42 concentrations decrease steadily with advancing disease progression [10, 35–38].”
Cerebrospinal fluid in the dementias
Zetterberg, H., Rohrer, J. D., & Schott, J. M. (2017) · Handbook of clinical neurology · doi:10.1016/b978-0-12-804279-3.00006-x · Cited by 13
Wierczeiko, A., Gammel, L., Radyushkin, K., Nguyen, V. T. T., Todorov, H., Gerber, S., & Endres, K. (2021) · Cells · doi:10.3390/cells10030693 · Cited by 11
Neurodegeneration Within the Amygdala Is Differentially Induced by Opioid and HIV-1 Tat Exposure
Nass, S. R., Ohene‐Nyako, M., Hahn, Y. K., Knapp, P. E., & Hauser, K. F. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.804774 · Cited by 12
Learning Continuous-Time Hidden Markov Models for Event Data
Liu, Y., Moreno, A., Li, S., Li, F., Song, L., & Rehg, J. M. (2017) · Springer eBooks · doi:10.1007/978-3-319-51394-2_19 · Cited by 11
Lindberg, O. E., Kern, S., Skoog, J., Machado, A., Pereira, J. B., Sacuiu, S. F., Wahlund, L., Blennow, K., Zetterberg, H., Zettergren, A., et al. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.10.033 · Cited by 10
Townsend, M. K., Okereke, O. I., Xia, W., Yang, T., Selkoe, D. J., & Grodstein, F. (2011) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31821764ce · Cited by 11
“Cerebral accumulation of Ab42 likely begins at least 10 to 15 years before the onset of clinical symptoms.(3,4) Therefore, identifying early determinants of Ab42 accumulation may lead to ways to help stem the growing epidemic of AD.”
BackgroundA lzheimer's Disease Biomarkers: More Than Molecular Diagnostics
Anderson, D. C. (2013) · Drug Development Research · doi:10.1002/ddr.21073 · Cited by 9
“…in the brain, are associated with brain atrophy (as measured by neuroimaging whole-brain volume) in preclinical AD, while increases in CSF tau and phospho-181 tau correlate with clinical onset/progression of AD and further structural brain damage [Fagan et al., 2009; Fjell et al., 2010].”
BackgroundKitajima, K., Abe, K., Takeda, M., Yoshikawa, H., Ohigashi, M., Osugi, K., Koyama, H., & Yamakado, K. (2021) · Medicine · doi:10.1097/md.0000000000023969 · Cited by 10
Wang, X., Wang, M., Wang, X., Zhou, F., Jiang, J., Liu, H., & Han, Y. (2021) · Brain Imaging and Behavior · doi:10.1007/s11682-021-00558-w · Cited by 9
Balasa, M., Dídac Vidal-piñeiro, A., Lladó, A., Antonell, A., Bosch, B., Castellanos, F., Bargalló, N., Bartrés‐Faz, D., Molinuevo, J. L., & Sánchez‐Valle, R. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111949 · Cited by 9
Burton, E. J., Mukaetova‐Ladinska, E. B., Perry, R. H., Jaros, E., Barber, R., & O'Brien, J. T. (2012) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.3774 · Cited by 10
“, 2010), whereas a study looking at amyloid in the cerebrospinal fluid as a biomarker found a correlation between beta amyloid and atrophy in non-demented subjects but not those with mild cognitive impairment or AD (Fagan et al., 2009).”
BackgroundAdriaanse, S. M., Dijk, K. R. A. V., Ossenkoppele, R., Reuter, M., Tolboom, N., Zwan, M. D., Yaqub, M. M., Boellaard, R., Windhorst, A. D., van der Flier, W. M., et al. (2014) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-014-2704-z · Cited by 9
Shin, H. S., Lee, S.-K., Kim, S., Kim, H.-J., Chae, W. S., & Park, S. A. (2016) · Dementia and Neurocognitive Disorders · doi:10.12779/dnd.2016.15.4.122 · Cited by 10
Xiong, C., Schindler, S. E., Henson, R. L., Wolk, D. A., Shaw, L. M. J., Agboola, F., Morris, J. C., Lu, R., & Luo, J. R. (2023) · Statistical Methods in Medical Research · doi:10.1177/09622802231215810 · Cited by 8
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Physics of Protein Aggregation in Normal and Accelerated Brain Aging
Espay, A. J., Sturchio, A., Imarisio, A., Hill, E. J., Williamson, B. J., Montemagno, K. T., Hoffmann, C., Roy, H. L., Milovanović, D., & Manfredsson, F. P. (2025) · BioEssays · doi:10.1002/bies.70030 · Cited by 9
Selkoe, D. J. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-410529-4.00067-x · Cited by 9
When Does Alzheimer’s Disease Really Start? The Role of Biomarkers
Lloret, A., Esteve, D., Lloret, M.-Á., Cervera‐Ferri, A., Lopez, B., Nepomuceno, M., & Monllor, P. (2021) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.19305 · Cited by 7
Beyond diagnosis: What biomarkers are teaching us about the “bio”logy of Alzheimer disease
Rabinovici, G. D., & Roberson, E. D. (2010) · Annals of Neurology · doi:10.1002/ana.22020 · Cited by 7
“Whereas Vemuri and colleagues propose that these events occur in sequence,(23) Chételat et al suggest that A may directly lead to neurodegeneration in the preclinical phase, with tangle-mediated neurodegeneration predominating later in the disease course.(16) Whichever proves to be true, perhaps the most important les…”
BackgroundSubcortical amyloid relates to cortical morphology in cognitively normal individuals
Rahayel, S., Bocti, C., Sévigny-Dupont, P., Joannette, M., Lavallée, M. M., Nikelski, J., Chertkow, H. M., & Joubert, S. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04446-w · Cited by 7
“In cognitively normal individuals, Aβ-related cortical volume changes, with increases being associated with frontal, temporal, cingulate, and parietal atrophy [10-14], or with”
BackgroundThe Diagnostic and Therapeutic Potential of Oligonucleotide Aptamers in Alzheimer’s Disease
Katsipis, G., Tzekaki, E. E., Iasonidou, S., & Pantazaki, Α. A. (2025) · Cells · doi:10.3390/cells14181424 · Cited by 6
Gasparini‐Berenguer, R., Monge-Argilés, J. A., Ruiz, C. M., Payá, J. S., Cantó, M. A. B., & Santana, C. L. (2014) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000025 · Cited by 6
Bioprofile Analysis: A New Approach for the Analysis of Biomedical Data in Alzheimer's Disease
Escudero, J., Initiative, A. D. N., Ifeachor, E., & Zajicek, J. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-121024 · Cited by 6
Mao, C., Sha, L., Li, J., Huang, X., Chu, S., Lei, D., Wang, J., Dong, L., Liu, C., Xu, Q., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210344 · Cited by 6
Adeyemi, O. F., Gowland, P. A., Bowtell, R. W., Mougin, O. E., & Hosseini, A. A. (2025) · European Journal of Neurology · doi:10.1111/ene.70076 · Cited by 7
Clinical Use of Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease
Zetterberg, H., Lunn, M. P., & Herukka, S. (2012) · Biomarkers in Medicine · doi:10.2217/bmm.12.47 · Cited by 5
Pradhan, S. S., Saiswaroop, R., Kanikaram, S. P., M., D. D. V., Pargaonkar, A., Dandamudi, R. B., & Sivaramakrishnan, V. (2023) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2023.2257322 · Cited by 5
“An inverse correlation is observed in the concentration of metabolites between the brain and blood or cerebrospinal fluid (Fagan et al., 2009; Kodam et al., 2023).”
Malpas, C. B., Saling, M. M., Velakoulis, D., Desmond, P. M., Hicks, R. J., Zetterberg, H., Blennow, K., & O'Brien, T. J. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170250 · Cited by 5
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Bagaria, J., Moon, Y., Bagyinszky, E., Shim, K. H., An, S. S. A., Kim, S., & Han, S. H. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.899644 · Cited by 4
New Diagnostic Criteria for Alzheimer‘s Disease
Zetterberg, H. (2011) · Biomarkers in Medicine · doi:10.2217/bmm.11.46 · Cited by 6
Scianatico, G., Manippa, V., Zacà, D., Jovicich, J., Tafuri, B., Rivolta, D., & Logroscino, G. (2024) · Current Alzheimer Research · doi:10.2174/0115672050330903240919074725 · Cited by 4
Ewers, M., Insel, P. S., Jagust, W. J., Shaw, L. M. J., Trojanowski, J. Q., Aisen, P. S. S., Petersen, R. C., Schuff, N. W., & Weiner, M. W. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2011.05.010 · Cited by 3
Should we lower or raise levels of amyloid-β in the brains of Alzheimer patients?
Imbimbo, B. P., Ippati, S., Imbimbo, C., & Balducci, C. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106390 · Cited by 4
Grey Matter and Cognitive Patterns in Cognitive Impaired Subjects Using CSF Biomarker Cut-Offs
Miralbell, J., Spulber, G., Hooshmand, B., Besga, A., Mataró, M., Cedazo-Mı́nguez, Á., Kivipelto, M., & Wahlund, L. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111553 · Cited by 3
Shin, K.-S., Kim, M. J., Lee, S. H., & Kang, J. Y. (2015) · IEEE International Conference on Micro Electro Mechanical Systems (MEMS) · doi:10.1109/memsys.2015.7051028 · Cited by 3
“Aβ has been usually measured using enzyme-linked immune sorbent assay (ELISA) but its sensitivity is not high enough to detect Aβ at levels below10 pg/ml [8, 9].”
MethodTapping into the biology of Alzheimer disease
Knopman, D. S. (2011) · Neurology · doi:10.1212/wnl.0b013e31820af995 · Cited by 3
Body Fluid Biomarkers of Neurological Injury in HIV-1-Associated Neurocognitive Disorder
Mei-juan, Y., Zhang, X., Zhang, D., Zhang, Y., Wang, J., Zhang, Y., Gu, C., Zhang, X., & Wei, L. (2025) · AIDS Research and Human Retroviruses · doi:10.1089/aid.2024.0053 · Cited by 2
CSF and serum total-tau and phospho-tau(181P) in MS patients
Jaworski, J., Psujek, M., & Bartosik-Psujek, H. (2011) · Open Medicine · doi:10.2478/s11536-011-0003-7 · Cited by 2
Snider, B. J., & Buckles, V. (2013) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/01.con.0000429171.50686.07 · Cited by 2
Alzheimer’s Disease and Other Neurodegenerative Disorders
Rosén, C., Zetterberg, H., & Blennow, K. (2015) · Springer eBooks · doi:10.1007/978-3-319-01225-4_20 · Cited by 2
Stomrud, E. (2009) · Lund University Publications (Lund University) · Cited by 2
Azargoonjahromi, A., & Initiative, A. D. N. (2025) · Journal of Molecular Neuroscience · doi:10.1007/s12031-025-02398-5 · Cited by 1
Ashraf, A., Mehta, P. D., & Edison, P. (2012) · Reviews in Clinical Gerontology · doi:10.1017/s0959259812000160 · Cited by 1
Brain MRI signatures across sex and CSF Alzheimer’s disease biomarkers
Cheng, Y., He, Y., Gopinath, K. K., Billot, B., Iglesias, J. E., Wu, C., Dodge, H. H., Wills, A.-M. A., Carlyle, B. C., Kivisäkk, P., et al. (2025) · Brain Communications · doi:10.1093/braincomms/fcaf210 · Cited by 1
“19 20-23 The revised Alzheimer’s disease diagnostic criteria high-light that amyloidosis is essentially a prerequisite of Alzheimer’s disease tauopathy, 3 underscoring the need to study how brain volumes associate with tau in the presence of amyloid.”
Cerebrospinal Fluid β-Amyloid 42, Tau, and P-tau
Holtzman, D. M. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.270 · Cited by 1
Self-citationVariación del péptido beta amiloide (1-42) en plasma en pacientes sometidos a anestesia.
Perucho, J., Ros, R., Arribas, P., Roux, D. P., de Yébenes, J. G., & Rubio, I. (2011) · Archivos de Medicina
Estudi de l'atròfia cerebral en la malaltia de l'Alzheimer
Pegueroles, J. (2014)
Tests, Tests, and More Tests: A New Era for Dementia Diagnosis
Gooblar, J. (2013) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k7ks6pqd
“Previous studies have examined the utility of CSF information in research settings, finding good diagnostic sensitivity and correlation with pathological markers of AD progression such as structural brain changes (Blennow, 2005; Fagan et al., 2009).”
BackgroundThe Role of Apolipoprotein E Concentration and Isoform in Amyloid-beta Metabolism In Vivo
Castellano, J. M. (2011) · Open Scholarship Institutional Repository (Washington University in St. Louis) · doi:10.7936/k7416v3s
“It is widely hypothesized that this finding reflects a process by which Aβ42 is sequestered into amyloid plaques, changing the equilibrium between brain and CSF pools of Aβ (Clark et al., 2003; Fagan et al., 2009; Hong et al., 2011; Sunderland et al., 2003).”
BackgroundBalasa, M. (2013) · Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona)
The 7th Leonard Berg Symposium, Part 2
Strobel, G. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100213
“to shrink with progressing illness [15].”
Metadata
- Authors
- Fagan, A. M., Head, D., Shah, A. R., Marcus, D., Mintun, M., Morris, J. C., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Fagan, Anne M.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2009-02
- Volume
- 65
- Issue
- 2
- Pages
- 176-183
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC2763631
- OpenAlex
- W2088129757
- Semantic Scholar
- 38dd6ce07732345d02e7f299e98dc24aad1252f6
- Cited by
- 327
- References
- 53
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 17 · 2020: 9 · 2019: 13 · 2018: 15 · 2017: 15 · 2016: 15 · 2015: 21 · 2014: 24 · 2013: 30 · 2012: 38
- FWCI
- 27.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000448)
- National Institute on Aging (P 50 AG05681, P50AG005681, P01 AG0 3991, P01AG003991, U19AG032438, P01AG026276)
- National Institute of Neurological Disorders and Stroke (P30NS057105, P30NS048056)
- National Center for Research Resources (UL1RR024992)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, cerebrospinal fluid biomarkers, amyloid-beta 42, Aβ40, tau protein, phosphorylated tau 181, brain atrophy, total brain volume, preclinical Alzheimer's disease, mild cognitive impairment, Alzheimer-type dementia, plasma amyloid-beta, CSF tau
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Aniline Compounds, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Peptide Fragments, Thiazoles, Geriatric Assessment, Chi-Square Distribution, Amyloid beta-Peptides, Pick Disease of the Brain, Positron-Emission Tomography
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