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]
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The Role of Genetics in Advancing Precision Medicine for Alzheimer’s Disease—A Narrative Review
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“Levels of CSF tau and ptau, but not Aβ42, were found to correlate with brain atrophy in AD (33).”
BackgroundEfficient Learning of Continuous-Time Hidden Markov Models for Disease Progression.
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Britschgi, M., Rufibach, K., Huang, S. L. B., Clark, C. M., Kaye, J. A., Li, G., Peskind, E. R., Quinn, J. F., Galasko, D. R., & Wyss‐Coray, T. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.008862 · Cited by 73
Deficits in Spontaneous Cognition as an Early Marker of Alzheimer’s Disease
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The NGF Metabolic Pathway in the CNS and its Dysregulation in Down Syndrome and Alzheimer's Disease
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Bertens, D., Knol, D. L., Scheltens, P., Visser, P. J., & Initiative, A. D. N. (2014) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2014.05.1754 · Cited by 70
“Other studies, however, reported cortical thinning in several cortical regions [25], and reduced whole brain and hippocampal volume [26,27].”
Nettiksimmons, J., Harvey, D. J., Brewer, J. B., Carmichael, O. T., DeCarli, C. S., Jack, C. R., Petersen, R. C., Shaw, L. M. J., Trojanowski, J. Q., Weiner, M. W., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.04.025 · Cited by 64
Biomarkers for Alzheimer's disease in plasma, serum and blood - conceptual and practical problems
Galasko, D. R., & Golde, T. E. (2013) · Alzheimer s Research & Therapy · doi:10.1186/alzrt164 · Cited by 64
The PSEN1, p.E318G Variant Increases the Risk of Alzheimer's Disease in APOE-ε4 Carriers
Benítez, B. A., Karch, C. M. M., Cai, Y., Jin, S. C., Cooper, B., Carrell, D., Bertelsen, S. E., Chibnik, L. B., Schneider, J. A., Bennett, D., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003685 · Cited by 68
Self-citationChoo, I. H., Carter, S. F., Schöll, M., & Nordberg, A. K. (2014) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-014-2859-7 · Cited by 63
Clinical impact of [18F]flutemetamol PET among memory clinic patients with an unclear diagnosis
Leuzy, A., Savitcheva, I., Chiotis, K., Lilja, J., Andersen, P., Bogdanović, N., Jelić, V., & Nordberg, A. K. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04297-5 · Cited by 60
Brown, L. A. M., Jin, J., Ferrell, D., Sadic, E., Obregon, D. F., Smith, A. J., Tan, J., & Giunta, B. N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095500 · Cited by 59
Gispert, J. D., Rami, L., Sánchez‐Benavides, G., Falcón, C., Tucholka, A., Rojas, S., & Molinuevo, J. L. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.06.027 · Cited by 56
Role of Family History for Alzheimer Biomarker Abnormalities in the Adult Children Study
Xiong, C. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.208 · Cited by 56
Lazarczyk, M. J., Hof, P. R., Bouras, C., & Giannakopoulos, P. (2012) · BMC Medicine · doi:10.1186/1741-7015-10-127 · Cited by 55
Blood-Based ATN Biomarkers of Alzheimer’s Disease: A Meta-Analysis
Koychev, I. G., Jansen, K., Dette, A., Shi, L., & Holling, H. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200900 · Cited by 59
Reliable Measurements of theβ-Amyloid Pool in Blood Could Help in the Early Diagnosis of AD
Pesini, P., Pérez‐Grijalba, V., Monleón, I., Boada, M., Tárraga, L., Martínez‐Lage, P., José, I. S., & Sarasa, M. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/604141 · Cited by 57
“Further experiments are needed to understand the circulation of Aβ between ISF, CSF, and blood as well as the relationship between biochemical and neuroimaging biomarkers [35, 42–46].”
BackgroundSynapses, synaptic activity and intraneuronal Aβ in Alzheimer’s disease
Tampellini, D. (2010) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2010.00013 · Cited by 58
D’Anna, L., Abu‐Rumeileh, S., Fabris, M., Pistis, C., Baldi, A., Sanvilli, N., Curcio, F., Gigli, G. L., D’Anna, S., & Valente, M. (2017) · Neurodegenerative Diseases · doi:10.1159/000474940 · Cited by 56
Bussy, A., Snider, B. J., Coble, D. W., Xiong, C., Fagan, A. M., Cruchaga, C., Benzinger, T. L. S., Gordon, B. A., Hassenstab, J. J., Bateman, R. J., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.10.011 · Cited by 57
“The DIAN study has been useful in this regard (Bateman et al., 2012; Benzinger et al., 2013; Cash et al., 2013; Fagan et al., 2014; Wang et al., 2015), as have large cohorts in sporadic AD, including the Alzheimer Disease Neuroimaging Initiative (ADNI, reviewed in Weiner et al., 2017), the Knight Alzheimer Disease Res…”
BackgroundSelf-citationToward a multifactorial model of Alzheimer disease
Storandt, M., Head, D. M., Fagan, A. M., Holtzman, D. M., & Morris, J. C. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.11.029 · Cited by 54
“This value was used previously to describe individuals as PIB positive (Fagan et al., 2009; Mintun et al, 2006) or having fibrillar amyloid plaque burden similar to those with AD.”
BackgroundMethodInfluentialSelf-citationAntonell, A., Fortea, J., Rami, L., Bosch, B., Balasa, M., Sánchez‐Valle, R., Iranzo, Á., Molinuevo, J. L., & Lladó, A. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0534-0 · Cited by 51
“…could hypothesise that controls with only Ab42 altered (group 2), could represent an earlier and longer phase than group with Ab42 plus t-tau and/or p-tau181 altered (group 3) of preclinical stage of AD (Jack et al. 2010; Stomrud et al. 2007; Fagan et al. 2009; Fagan et al. 2007; Li et al. 2007).”
BackgroundWang, L., Kang, H., Li, Y., Shui, Y., Yamamoto, R., Sugai, T., & Kato, N. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.12.033 · Cited by 51
Fjell, A. M., Idland, A., Sala‐Llonch, R., Watne, L. O., Borza, T., Brækhus, A., Lona, T., Zetterberg, H., Blennow, K., Wyller, T. B., et al. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx157 · Cited by 57
Ray, B., Reyes, P. F., & Lahiri, D. K. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.07.011 · Cited by 52
Plasma Aβ and PET PiB binding are inversely related in mild cognitive impairment
Devanand, D. P., Schupf, N., Stern, Y., Parsey, R. V., Pelton, G. H., Mehta, P. D., & Mayeux, R. P. (2011) · Neurology · doi:10.1212/wnl.0b013e318224afb7 · Cited by 50
Brain structure and function as mediators of the effects of amyloid on memory
Mattsson, N., Insel, P. S., Aisen, P. S. S., Jagust, W., Mackin, S. R., Weiner, M. W., Initiative, A. D. N., Weiner, M. W., Aisen, P. S. S., Weiner, M. W., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001375 · Cited by 52
Self-citationImproving CSF biomarker accuracy in predicting prevalent and incident Alzheimer disease
Roe, C. M., Fagan, A. M., Williams, M., Ghoshal, N., Aeschleman, M., Grant, E., Marcus, D. S., Mintun, M. A., Holtzman, D. M., & Morris, J. C. (2011) · Neurology · doi:10.1212/wnl.0b013e31820af900 · Cited by 49
Self-citationRevision of the criteria for Alzheimer's disease: A symposium
DeKosky, S. T., Carrillo, M. C., Phelps, C. H., Knopman, D. S., Petersen, R. C., Frank, R., Schenk, D., Masterman, D. M., Siemers, E., Cedarbaum, J. M., et al. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.12.007 · Cited by 52
Phosphorylated tau 231, memory decline and medial temporal atrophy in normal elders
Glodzik, L., Santi, S. D., Tsui, W. H., Mosconi, L., Zinkowski, R. P., Pirraglia, E., Wang, H. Y., Li, Y., Rich, K. E., Zetterberg, H., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.12.026 · Cited by 52
“Contrary, to a recent cross-sectional study of normal subjects (Fagan et al., 2009), we found baseline elevations of p- tau231, but not Aβ reductions associated with longitudinal MTL GM changes.”
BackgroundResultCortical atrophy in presymptomatic Alzheimer's disease presenilin 1 mutation carriers
Quiroz, Y. T., Stern, C. E., Reiman, E. M., Brickhouse, M. J., Ruiz‐Rizzo, A. L., Sperling, R. A., Lopera, F. J., & Dickerson, B. C. (2012) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-303299 · Cited by 50
Bubu, O. M., Umasabor‐Bubu, O. Q., Turner, A. D., Parekh, A., Mullins, A. E., Kam, K., Birckbichler, M. K., Mukhtar, F., Mbah, A. K., Williams, N. J., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12184 · Cited by 57
Dkk‐3 is elevated in CSF and plasma of Alzheimer’s disease patients
Zenzmaier, C., Marksteiner, J., Kiefer, A., Berger, P., & Humpel, C. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06158.x · Cited by 49
“Dickkopf homolog-3 as a diagnostic biomarker for dementia b-amyloid (1–42), one of the best established and widely used biomarkers for diagnosis of AD (Fagan et al. 2009; Shaw et al. 2009; Tapiola et al. 2009), segregates the studied cohorts with high sensitivity and specificity.”
BackgroundTimsina, J., Ali, M., Do, A. N., Wang, L., Western, D., Sung, Y. J., & Cruchaga, C. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106373 · Cited by 48
“Knight ADRC cohort ( N = 1044) but the estimated cutoff (527 pg/ml) was fairly close to the literature-derived threshold (500 pg/ml) for this platform (Fagan et al., 2009a).”
MethodPerrin, R. J., Payton, J. E., Malone, J. P., Erdmann-Gilmore, P., Davis, A., Xiong, C., Fagan, A. M., Townsend, R. R., & Holtzman, D. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064314 · Cited by 50
Self-citationQin, J., Jo, D., Cho, M., & Lee, Y. (2018) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2018.04.061 · Cited by 49
Keshavan, A., Wellington, H., Chen, Z., Khatun, A., Chapman, M. D., Hart, M., Cash, D. M., Coath, W., Parker, T. D., Buchanan, S. M., et al. (2021) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12131 · Cited by 49
Bouscary, A., Quessada, C., René, F., Spedding, M., Turner, B. J., Henriques, A., Ngo, S. T., & Loeffler, J. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.10.008 · Cited by 51
Cerebrospinal Fluid Biomarkers, Education, Brain Volume, and Future Cognition
Roe, C. M., Fagan, A. M., Grant, E., Marcus, D. S., Benzinger, T. L. S., Mintun, M. A., Holtzman, D. M., & Morris, J. C. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.192 · Cited by 50
Self-citationUpdate on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease
Leko, M. B., Štrac, D. Š., Mück‐Šeler, D., Pivac, N., Stanić, G., Hof, P. R., & Šimić, G. (2014) · Croatian Medical Journal · doi:10.3325/cmj.2014.55.347 · Cited by 48
Viscoelastic Properties of Human Autopsy Brain Tissues as Biomarkers for Alzheimer's Diseases
Park, K., Lonsberry, G. E., Gearing, M., Levey, A. I., & Desai, J. P. (2018) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2018.2878555 · Cited by 47
Han, X. (2010) · Molecular Neurobiology · doi:10.1007/s12035-009-8092-x · Cited by 47
Biomarkers of inflammation and amyloid-β phagocytosis in patients at risk of Alzheimer disease
Fiala, M., & Veerhuis, R. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.08.003 · Cited by 46
Neuroimaging of Alzheimer’s disease: focus on amyloid and tau PET
Matsuda, H., Shigemoto, Y., & Sato, N. (2019) · Japanese Journal of Radiology · doi:10.1007/s11604-019-00867-7 · Cited by 50
Silva, A. R. T., Grinberg, L. T., Farfel, J. M., Diniz, B. S., Lima, L. A., Silva, P. J. S., Ferretti, R. E. L., Rocha, R. M., Filho, W. J., Carraro, D. M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048751 · Cited by 40
Diagnostic biomarkers in Alzheimer’s disease
Andersen, E., Casteigne, B., Chapman, W. D., Creed, A., Foster, F., Lapins, A., Shatz, R., & Sawyer, R. P. (2021) · Biomarkers in Neuropsychiatry · doi:10.1016/j.bionps.2021.100041 · Cited by 42
Biomarkers for early detection of Alzheimer disease.
Barber, R. C. (2010) · PubMed · Cited by 41
Impaired β-Amyloid Secretion in Alzheimer's Disease Pathogenesis
Tampellini, D., Rahman, N., Lin, M. T. S., Capetillo‐Zarate, E., & Gouras, G. K. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2986-11.2011 · Cited by 41
Cerebrospinal fluid biomarkers for Alzheimerʼs disease
Zetterberg, H. (2015) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000179 · Cited by 42
Sala‐Llonch, R., Idland, A., Borza, T., Watne, L. O., Wyller, T. B., Brækhus, A., Zetterberg, H., Blennow, K., Walhovd, K. B., & Fjell, A. M. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161146 · Cited by 45
“While the role of YKL-40 in normal aging is almost unexplored, previous research on amyloid-related changes in the aging brain are conflicting, with some reporting more atrophy [19–21] in subjects with lower CSF A (cid:2) 42 levels and others larger volumes [22], or non-linear relationships [23].”
The Role of Diffusion Tensor Imaging in the Study of Cognitive Aging
Carmichael, O. T., & Lockhart, S. N. (2011) · Current topics in behavioral neurosciences · doi:10.1007/7854_2011_176 · Cited by 46
“These individuals may represent the earliest detectable stage of the AD pathology process: they already show subtle gross anatomical, functional, and neuropsychological deficits (Fagan et al. 2009; Sperling et al. 2009; Pike et al. 2007), and many of them are likely to develop clinical AD in the long term (Morris et a…”
BackgroundBiomarkers Predicting Alzheimer's Disease in Cognitively Normal Aging
Shim, Y. S., & Morris, J. C. (2011) · Journal of Clinical Neurology · doi:10.3988/jcn.2011.7.2.60 · Cited by 41
Self-citationAllison, S. L., Koscik, R. L., Cary, R. P., Jonaitis, E. M., Rowley, H. A., Chin, N. A., Zetterberg, H., Blennow, K., Carlsson, C. M., Asthana, S., et al. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101895 · Cited by 41
“…are commonly used in the field and prior literature has suggested all three are associated with structural changes in AD (Dickerson et al., 2011; Dickerson and Wolk, 2012; Fagan et al., 2009; Fox et al., 1999; Jack et al., 1992; Schott et al., 2010; Schwarz et al., 2016; Storandt et al., 2009).”
BackgroundVibrational spectroscopic analysis of peripheral blood plasma of patients with Alzheimer’s disease
Carmona, P., Molina, M., López‐Tobar, E., & Tolédano, A. (2015) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-015-8940-7 · Cited by 38
Schindler, S. E., & Fagan, A. M. (2015) · Frontiers in Neurology · doi:10.3389/fneur.2015.00142 · Cited by 40
Self-citationVariables associated with hippocampal atrophy rate in normal aging and mild cognitive impairment
Nosheny, R. L., Insel, P. S., Truran, D., Schuff, N. W., Jack, C. R., Aisen, P. S. S., Shaw, L. M. J., Trojanowski, J. Q., & Weiner, M. W. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.07.036 · Cited by 39
“Fibrillar A b deposition is associated with whole brain atrophy (Becker et al., 2011; Fagan et al., 2009), including hippocampal atrophy (Mormino et al., 2009) (Fjell et al., 2010; Schott et al., 2010; Storandt et al., 2009; Tosun et al., 2010) in older adult nondemented participants.”
Lack of association between 11C-PiB and longitudinal brain atrophy in non-demented older individuals
Driscoll, I. F., Zhou, Y., An, Y., Sojkova, J., Davatzikos, C. A., Kraut, M. A., Ye, W., Ferrucci, L., Mathis, C. A., Klunk, W. E., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.12.008 · Cited by 38
The expanding realm of prion phenomena in neurodegenerative disease
Frost, B. E., & Diamond, M. I. (2009) · Prion · doi:10.4161/pri.3.2.8754 · Cited by 36
Mizoi, M., Yoshida, M., Saiki, R., Waragai, M., Uemura, K., Akatsu, H., Kashiwagi, K., & Igarashi, K. (2014) · Clinica Chimica Acta · doi:10.1016/j.cca.2014.01.007 · Cited by 36
Alzheimer's disease — Recent biomarker developments in relation to updated diagnostic criteria
Höglund, K., Fourier, A., Perret‐Liaudet, A., Zetterberg, H., Blennow, K., & Portelius, E. (2015) · Clinica Chimica Acta · doi:10.1016/j.cca.2015.01.041 · Cited by 39
Laforce, R. J., Rosa‐Neto, P., Soucy, J., Rabinovici, G. D., Dubois, B., & Gauthier, S. G. (2016) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2015.401 · Cited by 34
Rai, N., Kumar, R. K., Desai, G. R., Gunasekaran, V., Shekhar, S., Chatterjee, P., Tripathi, M., Upadhyay, A. D., Dwivedi, S. N., Dey, A. B., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160479 · Cited by 34
“At present, the most validated AD biomarker is increased A (cid:2) levels in the cerebrospinal fluid (CSF) [5].”
Evaluation of dementia by acrolein, amyloid-β and creatinine
Igarashi, K., Yoshida, M., Waragai, M., & Kashiwagi, K. (2015) · Clinica Chimica Acta · doi:10.1016/j.cca.2015.07.017 · Cited by 35
Jaworski, J., Psujek, M., Janczarek, M., Szczerbo‐Trojanowska, M., & Bartosik-Psujek, H. (2012) · Upsala Journal of Medical Sciences · doi:10.3109/03009734.2012.669423 · Cited by 33
“The negative relation was strengthened in the context of regional cortical atrophy for t-tau (30), but also whole-brain atrophy for both t-tau and p-tau (38).”
BackgroundPaternicò, D., Galluzzi, S., Drago, V., Bocchio‐Chiavetto, L., Zanardini, R., Pedrini, L., Baronio, M., Amicucci, G., & Frisoni, G. B. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2011.10.003 · Cited by 34
Shue, F., White, L. J., Hendrix, R. D., Ulrich, J. D., Henson, R. L., Knight, W., Martens, Y. A., Wang, N., Roy, B., Starling, S. C., et al. (2024) · Science Advances · doi:10.1126/sciadv.adk3674 · Cited by 33
Self-citationRingman, J. M., Gylys, K. H., Medina, L. D., Fox, M., Kepe, V., Flores, D. L., Apostolova, L. G., Barrio, J. R., Small, G., Silverman, D. H. S., et al. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.10.039 · Cited by 35
“As studies in late-onset AD have found that diminished CSF Aβ appears to precede tau elevations[3], this may represent a distinction between the behavior of these markers in late-onset and familial AD.”
Disentangling the Amyloid Pathways: A Mechanistic Approach to Etiology
Malmberg, M., Malm, T., Gustafsson, O., Sturchio, A., Graff, C., Espay, A. J., Wright, A. P. H., Andaloussi, S. E., Lindén, A., & Ezzat, K. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00256 · Cited by 30
“In AD and PD, the decrease in CSF levels of soluble Aβ (Fagan et al., 2009; Bateman et al., 2012; Buchhave et al., 2012) and α-syn (Tokuda et al., 2006; Wang et al., 2015; Mollenhauer et al., 2019; Parnetti et al., 2019) is among the early biochemical markers of the disease.”
BackgroundBeta‐amyloid 1‐42 monomers, but not oligomers, produce PHF ‐like conformation of Tau protein
Manassero, G., Guglielmotto, M., Zamfir, R. I., Borghi, R., Colombo, L., Salmona, M., Perry, G. L., Odetti, P. R., Arancio, O., Tamagno, E., et al. (2016) · Aging Cell · doi:10.1111/acel.12500 · Cited by 32
“Its concentration in interstitial fluid is proportional to the level of global brain function (Fagan et al. , 2009).”
BackgroundBae, S., Lee, S., Harada, K., Makino, K., Chiba, I., Katayama, O., Shinkai, Y., Park, H., & Shimada, H. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9051424 · Cited by 31
“Structural MRI studies examining AD signatures have focused on global atrophy [33,34], hippocampal volume atrophy [35,36], and an AD signature consisting of a composite of thickness estimates derived from regions impacted early during the course of AD [37,38].”
BackgroundWang, L., Fagan, A. M., Shah, A. R., Beg, M. F., Csernansky, J. G., Morris, J. C., & Holtzman, D. M. (2011) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31823c0cf4 · Cited by 33
“The lack of correlation between CSF measures and initial hippocampal volumes was also found in a previously published study of a larger sample (from which this cohort has been obtained).(10) The relationships between CSF measures and rates of hippocampal surface deformation are visualized on the hippocampal surfaces w…”
MethodResultSelf-citationCognitive aging in persons with minimal amyloid-β and white matter hyperintensities
Nebes, R. D., Snitz, B. E., Cohen, A. D., Aizenstein, H. J., Saxton, J. A., Halligan, E. M., Mathis, C. A., Price, J. C., Kamboh, M. I., Weissfeld, L. A., et al. (2013) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2013.07.017 · Cited by 32
Biomarkers in Alzheimer’s Disease
Riverol, M., & López, O. L. (2011) · Frontiers in Neurology · doi:10.3389/fneur.2011.00046 · Cited by 33
Amyloid Imaging in Early Detection of Alzheimer’s Disease
Nordberg, A. K. (2010) · Neurodegenerative Diseases · doi:10.1159/000289223 · Cited by 33
Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer’s disease
Initiative, A. D. N., Ower, A. K., Hadjichrysanthou, C., Gras, L. A., Goudsmit, J., Anderson, R. M., & de Wolf, F. (2017) · European Journal of Epidemiology · doi:10.1007/s10654-017-0326-z · Cited by 31
Falcón, C., Tucholka, A., Monté, G. C., Cacciaglia, R., Operto, G., Rami, L., Gispert, J. D., & Molinuevo, J. L. (2018) · NeuroImage Clinical · doi:10.1016/j.nicl.2018.04.016 · Cited by 29
“In cross-sectional comparisons, amyloid positive non-demented subjects show decreased whole brain (Fagan et al., 2009) or hippocampal volumes (Bourgeat et al., 2010; Dickerson et al., 2009; Mormino et al., 2009; Storandt et al., 2009).”
CSF biomarkers of Alzheimer disease
Roe, C. M., Fagan, A. M., Grant, E., Holtzman, D. M., & Morris, J. C. (2013) · Neurology · doi:10.1212/01.wnl.0000436940.78152.05 · Cited by 29
Self-citationOue, H., Miyamoto, Y., Koretake, K., Okada, S., Doi, K., Jung, C., Michikawa, M., & Akagawa, Y. (2014) · Gerodontology · doi:10.1111/ger.12153 · Cited by 29
Cerebrospinal fluid Aβ levels correlate with structural brain changes in Parkinson's disease
Beyer, M. K., Alves, G. W., Hwang, K., Babakchanian, S., Brønnick, K., Chou, Y., Dalaker, T. O., Kurz, M. W., Larsen, J. O., Somme, J. H., et al. (2013) · Movement Disorders · doi:10.1002/mds.25282 · Cited by 28
Chang, C.-C., Althaus, J. C., Carruthers, C. J. L., Sutton, M. A., Steel, D. G., & Gafni, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082139 · Cited by 28
Kim, J.-H., Jung, Y., Kim, J.-W., Ha, M., Ha, S.-M., & Kim, D. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.03.024 · Cited by 28
Almdahl, I. S., Lauridsen, C., Selnes, P., Kalheim, L. F., Coello, C. S., Gajdzik, B., Møller, I., Wettergreen, M., Grambaitė, R., Bjørnerud, A., et al. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00009 · Cited by 27
“Similarly, Fagan et al. (2009) found that CSF Aβ42 correlated with whole-brain volume in elderly subjects without cognitive impairment, but not in MCI and AD, suggesting that the association between atrophy and amyloid could be present only early in the disease process.”
Recent Advances in Imaging Alzheimer's Disease
Braskie, M. N., Toga, A. W., & Thompson, P. M. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129016 · Cited by 26
“Cross-sectionally, CSF A 42 correlated with whole brain volumes in nondemented subjects, but in AD, CSF tau and phosphorylated tau were higher in those with smaller brains; this suggests that A toxicity may precede both clinical symptoms and changes in tau [129].”
Niedźwieńska, A., & Kvavilashvili, L. (2018) · Neuropsychology · doi:10.1037/neu0000457 · Cited by 29
“For example, several studies have found that amyloid depositions may be related to subsequent neurodegeneration in medial temporal lobes and surrounding areas at later stages of MCI (Fagan et al., 2009; Mormino et al., 2009).”
BackgroundHu, X., Meier, M., & Pruessner, J. C. (2023) · Brain and Behavior · doi:10.1002/brb3.2925 · Cited by 24
“The reason for the improved performance of Aβ42/Aβ40 ratio is still unclear, but it is hypothesized that Aβ40 can serve as an indicator of total Aβ and the ratio offsets the individual differences of total Aβ level in CSF (Lewczuk et al., 2015).”
BackgroundInfluentialCould Clinical Profile Influence CSF Biomarkers in Early-onset Alzheimer Disease?
Koric, L., Félician, O., Guedj, É., Hubert, A.-M., Mancini, J., Boucraut, J., & Ceccaldi, M. P. (2010) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e3181d712d9 · Cited by 26
“Decreased levels of the Ab42 variant have consistently been seen in the CSF of AD patients, even at very early stages of the disease.(39,40) Here, we found similar levels of CSF Ab42 in both groups.”
BackgroundCan MRI screen for CSF biomarkers in neurodegenerative disease?
McMillan, C. T., Avants, B., Irwin, D. J., Toledo, J. B., Wolk, D. A., Deerlin, V. M. V., Shaw, L. M. J., Trojanoswki, J. Q., & Grossman, M. (2012) · Neurology · doi:10.1212/wnl.0b013e31827b9147 · Cited by 24
“One case of autopsy-confirmed FTLD had CSF and MRI consistent with AD.”
BackgroundInfluentialRegional age-related atrophy after screening for preclinical alzheimer disease
Koenig, L. N., LaMontagne, P., Glasser, M. F., Bateman, R. J., Holtzman, D. M., Yakushev, I. Y., Chhatwal, J. P., Day, G. S., Jack, C. R., Mummery, C. J., et al. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.09.010 · Cited by 23
Self-citationKeshavan, A., Wellington, H., Chen, Z., Khatun, A., Chapman, M. D., Hart, M., Cash, D. M., Coath, W., Parker, T. D., Buchanan, S. M., et al. (2020) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12097 · Cited by 24
Clinical Neuroproteomics and Biomarkers
Shoemaker, L. D., Achrol, A. S., Sethu, P., Steinberg, G. K., & Chang, S. D. (2011) · Neurosurgery · doi:10.1227/neu.0b013e3182333a26 · Cited by 24
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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