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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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24 Own result · 9 Not checked yet · 6 Own method · 5 Own interpretation
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:
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- 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
plain- Asserted: passes — The authors put it forward as true.
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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
plaincorrelationaln = 26 ·- Asserted: passes — The authors put it forward as true.
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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
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“ptau181 (r=−0.0020, p=0.987)”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“tau (Fig. 1C)”
§ Decreased CSF Aβ42 correlates with brain atrophy in cognitively normal elderly > Results
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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:
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“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
plainn = 29- Asserted: passes — The authors put it forward as true.
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- 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
plainn = 29- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably 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
plain- Asserted: passes — The authors put it forward as true.
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Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably 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
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It 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
plaincorrelationaln = 29- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
hedgedconditionalSingle case- Asserted: passes — The authors put it forward as true.
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It 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably 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
plain- Asserted: passes — The authors put it forward as true.
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Probably 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:
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It 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
plainn = 98- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
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Probably 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
plainn = 98- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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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Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
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Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease
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McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657
“A sequence of events has been described with Aβ pathophysiological processes becoming abnormal first and downstream neuronal injury biomarkers becoming abnormal later [6,7], This might imply a hierarchical ranking of Aβ biomarkers over downstream neuronal injury McKhann et al.”
BackgroundSelf-citationHypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806
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Alzheimer’s Disease Neuroimaging Initiative
Mueller, S. G., Weiner, M. W., Thal, L. J., Petersen, R. C., Jack, C. R., Jagust, W. J., Trojanowski, J. Q., Toga, A. W., & Beckett, L. A. (2007) · Springer eBooks · doi:10.1007/978-0-387-72076-0_18 · Cited by 1,493
Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,242
“Given that a CSF Ab42 concentration lower than 500 pg/ml has been used as a reliable threshold for the presence of cerebral Ab deposition in humans (7, 19, 22, 26), we determined the proTable 1.”
Self-citationCSF Biomarkers and Incipient Alzheimer Disease in Patients With Mild Cognitive Impairment
Mattsson, N. (2009) · JAMA · doi:10.1001/jama.2009.1064 · Cited by 1,176
Biomarker Modeling of Alzheimer’s Disease
Jack, C. R., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.12.003 · Cited by 1,002
Self-citationAPOE predicts amyloid‐beta but not tau Alzheimer pathology in cognitively normal aging
Morris, J. C., Roe, C. M., Xiong, C., Fagan, A. M., Goate, A. M., Holtzman, D. M., & Mintun, M. A. (2010) · Annals of Neurology · doi:10.1002/ana.21843 · Cited by 830
“Data from many of the 241 participants have appeared in previous reports from our ADRC.(20,61,67)”
ResultInfluentialSelf-citationMultimodal techniques for diagnosis and prognosis of Alzheimer's disease
Perrin, R. J., Fagan, A. M., & Holtzman, D. M. (2009) · Nature · doi:10.1038/nature08538 · Cited by 702
Self-citationJack, C. R., Knopman, D. S., Weigand, S. D., Wiste, H. J., Vemuri, P., Lowe, V., Kantarci, K., Gunter, J. L., Senjem, M. L., Ivnik, R. J., et al. (2012) · Annals of Neurology · doi:10.1002/ana.22628 · Cited by 602
“[%] 94 [49] 35 [50] 19 [34] 6 [46] 41 [40] 10 [67]”
Johnson, K. A., Minoshima, S., Bohnen, N. I., Donohoe, K. J., Foster, N. L., Herscovitch, P., Karlawish, J. H., Rowe, C. C., Carrillo, M. C., Hartley, D. M., et al. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2013.01.002 · Cited by 603
Functional Alterations in Memory Networks in Early Alzheimer’s Disease
Sperling, R. A., Dickerson, B. C., Pihlajamaki, M. M., Vannini, P., LaViolette, P. S., Vitolo, O. V., Hedden, T., Becker, J. A., Rentz, D. M., Selkoe, D. J., et al. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8109-7 · Cited by 617
“…studies have provided support for the hypothesis that amyloid is an early upstream pathological event, which is related to subsequent neurodegeneration and atrophy in the MTL and surrounding cortices at later stages of prodromal AD (Mormino et al. 2008; Fagan et al. 2009; Jack et al. 2009).”
BackgroundPrediction of MCI to AD conversion, via MRI, CSF biomarkers, and pattern classification
Davatzikos, C. A., Bhatt, P., Shaw, L. M. J., Batmanghelich, K. N., & Trojanowski, J. Q. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.05.023 · Cited by 596
“…recent studies have suggested that early changes of the SPARE-AD scores and other morphological measurements, as well as CSF biomarkers, in cognitively normal elderly are good predictors of future progression to MCI (Davatzikos et al., 2008a, 2008b, 2009; Driscoll et al., 2009; Fagan et al., 2009).”
Brier, M. R., Thomas, J. B., Snyder, A. Z., Benzinger, T. L., Zhang, D., Raichle, M. E., Holtzman, D. M., Morris, J. C., & Ances, B. M. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5698-11.2012 · Cited by 595
Self-citationVerghese, P. B., Castellano, J. M., Garai, K., Wang, Y., Jiang, H., Shah, A., Bu, G., Frieden, C., & Holtzman, D. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220484110 · Cited by 556
“S1), a ratio similar to the Aβ40:42 ratio found in human CSF in normal subjects and in patients with late-onset AD (37, 38).”
BackgroundResultInfluentialSelf-citationMorris, J. C., Roe, C. M., Grant, E. A., Head, D., Storandt, M., Goate, A. M., Fagan, A. M., Holtzman, D. M., & Mintun, M. A. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.269 · Cited by 476
“Data from many of the 159 participants have appeared in other reports from our Alzheimer’s Disease Research Center.”
ResultSelf-citationJack, C. R., Wiste, H. J., Vemuri, P., Weigand, S. D., Senjem, M. L., Zeng, G., Bernstein, M. A., Gunter, J. L., Pankratz, V. S., Aisen, P. S., et al. (2010) · Brain · doi:10.1093/brain/awq277 · Cited by 531
Blood-Based Protein Biomarkers for Diagnosis of Alzheimer Disease
Doecke, J. D. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.1282 · Cited by 422
Brain β-amyloid load approaches a plateau
Jack, C. R., Wiste, H. J., Lesnick, T. G., Weigand, S. D., Knopman, D. S., Vemuri, P., Pankratz, V. S., Senjem, M. L., Gunter, J. L., Mielke, M. M., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e3182840bbe · Cited by 406
La Joie, R., Perrotin, A., Barré, L., Hommet, C., Mézenge, F., Ibazizene, M., Camus, V., Abbas, A., Landeau, B., Guilloteau, D., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.2170-12.2012 · Cited by 374
Relationship between atrophy and β‐amyloid deposition in Alzheimer disease
Chételat, G., Villemagne, V. L., Bourgeat, P., Pike, K. E., Jones, G., Ames, D., Ellis, K. A., Szoeke, C., Martins, R. N., O'Keefe, G. J., et al. (2010) · Annals of Neurology · doi:10.1002/ana.21955 · Cited by 373
“Our findings are similar to a recent study reporting correlation between cerebrospinal fluid A 42 and whole-brain atrophy in nondemented control subjects but not in AD (where atrophy was related to levels of cerebrospinal fluid tau).(25) Second, atrophy in SCI is related to local -amyloid deposition in areas of highes…”
ResultPreventing Alzheimer’s Disease
Selkoe, D. J. (2012) · Science · doi:10.1126/science.1228541 · Cited by 391
Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease
Gouras, G. K., Tampellini, D., Takahashi, R. H., & Capetillo-Zarate, E. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0679-9 · Cited by 372
Fagan, A. M., Mintun, M. A., Shah, A. R., Aldea, P., Roe, C. M., Mach, R. H., Marcus, D., Morris, J. C., & Holtzman, D. M. (2009) · EMBO Molecular Medicine · doi:10.1002/emmm.200900048 · Cited by 353
“Therefore, the mean age of our cohort is younger (64.7 10.4) than what we have reported on previously (71.41 8.62; Fagan et al, 2009).”
BackgroundMethodResultInfluentialSelf-citationThe Dynamics of Cortical and Hippocampal Atrophy in Alzheimer Disease
Sabuncu, M. R. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.167 · Cited by 339
Can Alzheimer disease be prevented by amyloid-β immunotherapy?
Lemere, C. A., & Masliah, E. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.219 · Cited by 351
Exercise and Alzheimer’s disease biomarkers in cognitively normal older adults
Liang, K. Y., Mintun, M. A., Fagan, A. M., Goate, A. M., Bugg, J. M., Holtzman, D. M., Morris, J. C., & Head, D. (2010) · Annals of Neurology · doi:10.1002/ana.22096 · Cited by 340
Self-citationJohnson, K. A., Minoshima, S., Bohnen, N. I., Donohoe, K. J., Foster, N. L., Herscovitch, P., Karlawish, J. H., Rowe, C. C., Carrillo, M. C., Hartley, D. M., et al. (2013) · Journal of Nuclear Medicine · doi:10.2967/jnumed.113.120618 · Cited by 329
Antisense Reduction of Tau in Adult Mice Protects against Seizures
DeVos, S. L., Goncharoff, D. K., Chen, G., Kebodeaux, C. S., Yamada, K., Stewart, F. R., Schuler, D. R., Maloney, S. E., Wozniak, D. F., Rigo, F., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2107-13.2013 · Cited by 311
Self-citationStorandt, M., Mintun, M. A., Head, D. M., & Morris, J. C. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.272 · Cited by 309
Self-citationQualification of the analytical and clinical performance of CSF biomarker analyses in ADNI
Initiative, T. A. D. N., Shaw, L. M. J., Vanderstichele, H., Knapik-Czajka, M. E., Figurski, M., Coart, E., Blennow, K., Soares, H. D., Simon, A. J., Lewczuk, P., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0808-0 · Cited by 301
“Measurement of the CSF concentrations of Ab1–42, t-tau and p-tau181 [using xMAP (multi-analyte) or ELISA (single analyte)-based methods] has been shown to provide at least 85% sensitivity and 80% specificity for diagnosing AD, predicting conversion from MCI to a diagnosis of probable AD, and identifying elderly clinic…”
MethodHead (2012) · doi:10.1001/archneurol.2011.845 · Cited by 267
Role of structural MRI in Alzheimer's disease
Vemuri, P., & Jack, C. R. (2010) · Alzheimer s Research & Therapy · doi:10.1186/alzrt47 · Cited by 265
“While some studies claim that there is an association between CSF biomarkers (specifi cally t-tau and p-tau) and sMRI [42,46,48-54], others have found no association between the two [45,55-57].”
BackgroundMRI cortical thickness biomarker predicts AD-like CSF and cognitive decline in normal adults
Dickerson, B. C., & Wolk, D. A. (2011) · Neurology · doi:10.1212/wnl.0b013e31823efc6c · Cited by 257
McKhann, G. M., Knopman, D. S., Chertkow, H. M., Hyman, B. T., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mohs, R. C., Morris, J. C., et al. (2011) · Alzheimer s & Dementia · Cited by 240
Self-citation(ADNI), A. D. N. I., Deming, Y., The Alzheimer Disease Genetic Consortium (ADGC), Li, Z., Kapoor, M., Harari, O., Del-Aguila, J. L., Black, K., Carrell, D., Cai, Y., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1685-y · Cited by 231
“Low Aβ42 levels (ADRC < 500 pg/mL and ADNI < 192 pg/ mL) have been associated with amyloid positron emission tomography (PET-PIB) evidence of Aβ deposition [25, 69].”
BackgroundResultInfluentialSelf-citationAmyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later
Roe, C. M., Fagan, A. M., Grant, E. A., Hassenstab, J., Moulder, K. L., Maue Dreyfus, D., Sutphen, C. L., Benzinger, T. L. S., Mintun, M. A., Holtzman, D. M., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e3182918ca6 · Cited by 222
Self-citationEvidence for Ordering of Alzheimer Disease Biomarkers
Jack, C. R. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.183 · Cited by 225
“80 81-86 Our results concerning evidence for biomarker ordering led to similar conclusions in the “all-participants” sample and in thesampleofparticipantswithanabnormalCSFA (cid:2) 42level.”
Cerebrospinal fluid APOE levels: an endophenotype for genetic studies for Alzheimer's disease
Cruchaga, C., Kauwe, J. S. K., Nowotny, P., Bales, K., Pickering, E. H., Mayo, K., Bertelsen, S., Hinrichs, A., Fagan, A. M., Holtzman, D. M., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds296 · Cited by 207
Self-citationHong, S., Ostaszewski, B. L., Yang, T., O’Malley, T. T., Jin, M., Yanagisawa, K., Li, S., Bartels, T., & Selkoe, D. J. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.027 · Cited by 213
“In light of numerous such studies implicating a pathogenic role of soluble Ab oligomers and the evidence that lowered Ab42 monomer levels in cerebrospinal fluid (CSF) represents the earliest biomarker for AD (Bateman et al., 2012; Craig-Schapiro et al., 2009; Fagan et al., 2009; Golde et al., 2011; Morris and Selkoe,…”
Fluid Biomarkers in Alzheimer Disease
Blennow, K., Zetterberg, H., & Fagan, A. M. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006221 · Cited by 208
“Further, although no study has examined the added diagnostic value of PIB-PET and CSF biomarkers, there is a strict negative correlation between the degree of PIB binding as seen in PET images and the CSF level of Ab42 (Fagan et al. 2006, 2009b; Forsberg et al. 2008; Grimmer et al. 2009).”
BackgroundResultInfluentialSelf-citationCairns, N. J., Ikonomović, M. D., Benzinger, T. L. S., Storandt, M., Fagan, A. M., Shah, A. R., Taylor‐Reinwald, L., Carter, D. R., Felton, A., Holtzman, D. M., et al. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.279 · Cited by 205
Self-citationAgreement of amyloid PET and CSF biomarkers for Alzheimer's disease on Lumipulse
Alcolea, D., Pegueroles, J., Muñoz, L., Camacho, V., López‐Mora, D., Fernández‐León, A., Le Bastard, N., Huyck, E., Nadal, A., Olmedo, V., et al. (2019) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.50873 · Cited by 183
Bourgeat, P., Chételat, G., Villemagne, V. L., Fripp, J., Raniga, P., Pike, K., Acosta, O., Szoeke, C., Ourselin, S., Ames, D., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e3181c918b5 · Cited by 220
Longitudinal Change of Biomarkers in Cognitive Decline
Lo, R. Y. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.123 · Cited by 197
CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease
Clifford, D. B., Fagan, A. M., Holtzman, D. M., Morris, J. C., Teshome, M., Shah, A. R., & Kauwe, J. S. K. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c5b445 · Cited by 186
Self-citationPET amyloid-beta imaging in preclinical Alzheimer's disease
Vlassenko, A. G., Benzinger, T. L. S., & Morris, J. C. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.11.005 · Cited by 188
Self-citationPerrin, R. J., Craig‐Schapiro, R., Malone, J. P., Shah, A. R., Erdmann-Gilmore, P., Davis, A., Roe, C. M., Peskind, E. R., Li, G., Galasko, D. R., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016032 · Cited by 175
Self-citationChen, K., Langbaum, J. B. S., Fleisher, A., Ayutyanont, N., Reschke, C., Lee, W., Liu, X., Bandy, D., Alexander, G. E., Thompson, P. M., et al. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.02.064 · Cited by 173
Detection and treatment of Alzheimer’s disease in its preclinical stage
Rafii, M. S., & Aisen, P. S. S. (2023) · Nature Aging · doi:10.1038/s43587-023-00410-4 · Cited by 179
Visinin‐like protein‐1: Diagnostic and prognostic biomarker in Alzheimer disease
Tarawneh, R. M., D’Angelo, G., Macy, E., Xiong, C., Carter, D. R., Cairns, N. J., Fagan, A. M., Head, D. M., Mintun, M. A., Ladenson, J. H., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22448 · Cited by 169
“Blood samples (10–15ml) were obtained from a subset of participants (CNC, n 1⁄4 149 and AD, n 1⁄4 64) and processed to obtain plasma as described.(29)”
MethodSelf-citationIndicators of amyloid burden in a population-based study of cognitively normal elderly
Mielke, M. M., Wiste, H. J., Weigand, S. D., Knopman, D. S., Lowe, V. J., Roberts, R. O., Geda, Y. E., Swenson-Dravis, D. M., Boeve, B. F., Senjem, M. L., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e31826e2696 · Cited by 163
Barthélemy, N. R., Mallipeddi, N., Moiseyev, P., Sato, C., & Bateman, R. J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00121 · Cited by 152
“T111, T205, S208 and T217 were more hyperphosphorylated than T181, which is the most commonly measured target used as a p-tau biomarker for AD (Fagan et al., 2009).”
BackgroundIncreased brain atrophy rates in cognitively normal older adults with low cerebrospinal fluid Aβ1‐42
Schott, J. M., Bartlett, J. W., Fox, N. C., Barnes, J., & Initiative, A. D. N. (2010) · Annals of Neurology · doi:10.1002/ana.22315 · Cited by 146
Ushering in the study and treatment of preclinical Alzheimer disease
Langbaum, J. B. S., Fleisher, A., Chen, K., Ayutyanont, N., Lopera, F. J., Quiroz, Y. T., Caselli, R. J., Tariot, P. N., & Reiman, E. M. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.107 · Cited by 149
Shapes of the Trajectories of 5 Major Biomarkers of Alzheimer Disease
Jack, C. R., Vemuri, P., Wiste, H. J., Weigand, S. D., Lesnick, T. G., Lowe, V., Kantarci, K., Bernstein, M. A., Senjem, M. L., Gunter, J. L., et al. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.3405 · Cited by 145
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Oh, J., Yoo, G., Chang, Y. W., Kim, H. J., Jose, J., Kim, E., Pyun, J., & Yoo, K. (2013) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2013.07.004 · Cited by 139
Novel plasma biomarker surrogating cerebral amyloid deposition
KANEKO, N., Nakamura, A., Washimi, Y., Kato, T., Sakurai, T., Arahata, Y., Bundo, M., Takeda, A., Niida, S., Ito, K., et al. (2014) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.90.353 · Cited by 138
3D PIB and CSF biomarker associations with hippocampal atrophy in ADNI subjects
Apostolova, L. G., Hwang, K., Andrawis, J. P., Green, A. E., Babakchanian, S., Morra, J. H., Cummings, J. L., Toga, A. W., Trojanowski, J. Q., Shaw, L. M. J., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.05.003 · Cited by 144
Canine Cognitive Dysfunction and Alzheimer’s Disease – Two Facets of the Same Disease?
Mihevc, S. P., & Majdič, G. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00604 · Cited by 152
Plasma Amyloid-β as a Biomarker in Alzheimer's Disease: The AIBL Study of Aging
Lui, J. K., Laws, S. M., Li, Q., Villemagne, V. L., Ames, D. J., Brown, B. M., Bush, A. I., Ruyck, K. D., Dromey, J. R., Ellis, K. A., et al. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-090249 · Cited by 136
“A decline in A β levels in the cerebrospinal fluid (CSF) has been reported to help distinguish between patients with AD and normal elderly individuals [4–8].”
When Does Alzheimer′s Disease Really Start? The Role of Biomarkers
Lloret, A., Esteve, D., Lloret, M.-A., Cervera-Ferri, A., Lopez, B., Nepomuceno, M., & Monllor, P. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225536 · Cited by 131
“Therefore, PiB-PET is only recommended when other clinical evidences of dementia are present [19,26], even though it is considered a valid marker to help in the diagnosis [51].”
BackgroundLeuzy, A., Chiotis, K., Hasselbalch, S. G., Rinne, J. O., de Mendonça, A., Otto, M., Lleó, A., Castelo-Branco, M. S., Santana, I. J., Johansson, J. J., et al. (2016) · Brain · doi:10.1093/brain/aww160 · Cited by 135
Cruchaga, C., Kauwe, J. S. K., Mayo, K., Spiegel, N., Bertelsen, S., Nowotny, P., Shah, A. R., Abraham, R., Hollingworth, P., Harold, D., et al. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001101 · Cited by 128
“This is likely to be true for Alzheimer’s Disease (AD) because up to 30% of individuals in screened elderly non-demented control samples show evidence of AD pathology at autopsy [12], and a similar number have biomarker profiles consistent with preclinical AD [13–15], thus reducing the power of a case-control design.”
BackgroundSelf-citationYang, T., Hong, S. Y., O’Malley, T. T., Sperling, R. A., Walsh, D. M., & Selkoe, D. J. (2013) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.11.005 · Cited by 122
Exercise Intervention Associated with Cognitive Improvement in Alzheimer’s Disease
Cui, M. Y., Lin, Y., Sheng, J. Y., Zhang, X., & Cui, R. (2018) · Neural Plasticity · doi:10.1155/2018/9234105 · Cited by 139
“This may be due to the participant of the research whom was in the early stage of cognitive decline while ptau is largely formed in the later course of AD [103].”
BackgroundCSF tau markers are correlated with hippocampal volume in Alzheimer's disease
de Souza, L. C., Marie Chupin, A., Lamari, F., Jardel, C., Leclercq, D., Olivier Colliot, A., Lehéricy, S., Dubois, B., & Sarazin, M. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.02.022 · Cited by 125
Biomarkers in Alzheimer's disease drug development
Cummings, J. L. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.06.004 · Cited by 122
Prevalence of preclinical Alzheimer disease
Kern, S., Zetterberg, H., Kern, J., Zettergren, A., Wærn, M., Höglund, K., Andréasson, U., Wetterberg, H., Börjesson‐Hanson, A., Blennow, K., et al. (2018) · Neurology · doi:10.1212/wnl.0000000000005476 · Cited by 123
Alzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics
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“For example, it is well known that elderly nondemented controls may show evidence of biochemical AD pathology postmortem (Price et al. 2009) or CSF alterations of Aβ before AD symptoms become manifest (Fagan et al. 2009).”
Serial MRI and CSF biomarkers in normal aging, MCI, and AD
Vemuri, P., Wiste, H. J., Weigand, S. D., Knopman, D. S., Trojanowski, J. Q., Shaw, L. M., Bernstein, M. A., Aisen, P. S., Weiner, M., Petersen, R. C., et al. (2010) · Neurology · doi:10.1212/wnl.0b013e3181e7ca82 · Cited by 154
Mormino, E. C., & Papp, K. V. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179928 · Cited by 124
“This observation has consistently been observed in postmortem studies [6, 16], CSF studies [17, 18], and Amyloid PET imaging studies [19].”
Brain Ventricular Volume and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease
Ott, B. R., Initiative, T. A. D. N., Cohen, R. A., Gongvatana, A., Okonkwo, O. C., Johanson, C. E., Stopa, E. G., Donahue, J. E., & Silverberg, G. D. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1406 · Cited by 117
Hong, S., Quintero-Monzon, O., Ostaszewski, B. L., Podlisny, D. R., Cavanaugh, W. T., Yang, T., Holtzman, D. M., Cirrito, J. R., & Selkoe, D. J. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3272-11.2011 · Cited by 111
Self-citationMelah, K. E., Lu, S. Y.-F., Hoscheidt, S. M., Alexander, A. L., Adluru, N., Destiche, D. J., Carlsson, C. M., Zetterberg, H., Blennow, K., Okonkwo, O. C., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150897 · Cited by 109
Fortea, J., Sala‐Llonch, R., Bartrés‐Faz, D., Lladó, A., Solé‐Padullés, C., Bosch, B., Antonell, A., Olives, J., Sánchez‐Valle, R., Molinuevo, J. L., et al. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.02.017 · Cited by 112
Is amyloid-β harmful to the brain? Insights from human imaging studies
Jagust, W. (2016) · Brain · doi:10.1093/brain/awv326 · Cited by 110
“CSF measures of amyloid-b1–42 have also been associated with whole brain atrophy (Fagan et al., 2009).”
BackgroundLongitudinal brain structural changes in preclinical Alzheimer's disease
Pegueroles, J., Vilaplana, E., Montal, V., Sampedro, F., Alcolea, D. A., Carmona‐Iragui, M., Clarimón, J., Blesa, R., Lleó, A., Fortea, J., et al. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.08.010 · Cited by 106
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Fluid and PET biomarkers for amyloid pathology in Alzheimer's disease
Cohen, A. D., Landau, S. M., Snitz, B. E., Klunk, W. E., Blennow, K., & Zetterberg, H. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.12.004 · Cited by 112
“Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease.”
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Brain Atrophy in Healthy Aging Is Related to CSF Levels of Aβ1-42
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“Theone large study of the relationship between the CSF biomarkers and brain volume found a relationship between low levels of A b 1-42 and smaller whole-brain volumes (Fagan et al. 2009).”
The Beta Amyloid Dysfunction (BAD) Hypothesis for Alzheimer’s Disease
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“Early biochemical deviations from Aβ physiology in MCI are indicated by lowered CSF Aβ42 monomer already before substantial loss of neurons occurs in later stages of AD (Fagan et al., 2009).”
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“…few MRI studies so far have reported correlations between CSF biomarkers and the pattern of brain atrophy or the rate of atrophy progression (Fagan et al., 2009; Fjell et al., 2010a, 2010b; Hampel et al., 2005; Hen-neman et al., 2009; Herukka et al., 2008; Leow et al., 2009; Schuff et al.,…”
Elevated cerebrospinal fluid sphingomyelin levels in prodromal Alzheimer's disease
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“stage, before PET imaging becomes abnormal [32],”
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Alzheimer’s Disease Biomarkers and Future Decline in Cognitive Normal Older Adults
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Alcolea, D. A., Vilaplana, E., Pegueroles, J., Montal, V., Sánchez‐Juan, P., González‐Suárez, A., Pozueta, A., Rodríguez‐Rodríguez, E., Bartrés‐Faz, D., Dídac Vidal-piñeiro, A., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.03.001 · Cited by 90
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Cerebrospinal Fluid Biomarkers of Alzheimer's Disease
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Self-citation11C-PiB Imaging of Human Immunodeficiency Virus–Associated Neurocognitive Disorder
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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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