Decreased cerebrospinal fluid Aβ 42 correlates with brain atrophy in cognitively normal elderly

In the paper

“with no change in mean levels of CSF Aβ40 or plasma Aβ40 or Aβ42.”

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”

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

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”

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

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”

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

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”

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

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.”

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

In the paper

“As chronological age was associated with fluid and imaging measures, correlations were adjusted for age in all analyses.”

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.”

In the paper

“the CSF tau/Aβ42 ratio predicts future cognitive decline in cognitively normal elders 34, 50 and individuals with MCI,51”

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

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).”

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.”

In the paper

“has been reported to generate volumes with a high correspondence to manually generated volumes. 31”

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

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.”

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

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.”

In the paper

“LP/blood collection and MRI were performed within 2 years of each other.”

In the paper

“CSF samples were free from any blood contamination.”

In the paper

“Hippocampal volumes were obtained from all but 12 of the 98 subjects (omissions due to Freesurfer processing errors).”