Plasma and Cerebrospinal Fluid Levels of Amyloid β Proteins 1-40 and 1-42 in Alzheimer Disease

Mehta, Pankaj; Pirttilä, Tuula; Mehta, Sangita P.; Sersen, Eugene A.; Aisen, Paul S.; Wı́sniewski, Henryk M.

doi:10.1001/archneur.57.1.100

Cited by 531 publications

(420 citation statements)

References 37 publications

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“…In this study, we demonstrated that OVX for 5 weeks increased Aβ 1-40 level in serum prepared from ICR female mice at 13-14 weeks old. In accordance with our finding, several clinical studies have demonstrated that plasma Aβ 1-40 level is elevated in sporadic AD (Mayeux et al, 2003;Mehta et al, 2000) and that platelets are the major contributor of peripherally generated Aβ to the plasma (Colciaghi et al, 2004). Such abnormalities in the platelet amyloid precursor protein (APP) metabolism are observed in patients with mild cognitive impairment, as well as Alzheimer's disease (Padovani et al, 2002).…”

Section: Discussionsupporting

confidence: 91%

Ovariectomy increases neuronal amyloid-β binding alcohol dehydrogenase level in the mouse hippocampus

Fukuzaki

Takuma

Funatsu

et al. 2008

Neurochemistry International

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Ovarian hormone decline after menopause may influence cognitive performance and increase the risk for Alzheimer's disease (AD) in women. Amyloid-β peptide (Aβ) has been proposed to be the primary cause of AD. In this study, we examined whether ovariectomy (OVX) could affect the levels of cofactors Aβ-binding alcohol dehydrogenase (ABAD) and receptor for advanced glycation endproducts (RAGE), which have been reported to potentiate Aβ-mediated neuronal perturbation, in mouse hippocampus, correlating with estrogen and Aβ levels. Female ICR mice were randomly divided into ovariectomized or sham-operated groups, and biochemical analyses were carried out at 5 weeks after the operation. OVX for 5 weeks significantly decreased hippocampal 17β-estradiol level, while it tended to reduce the hormone level in serum, compared with the sham-operated control. In contrast, OVX did not affect hippocampal Aβ 1-40 level, although it significantly increased serum Aβ 1-40 level. Furthermore, we demonstrated that OVX increased hippocampal ABAD level in neurons, but not astrocytes, while it did not affect RAGE level. These findings suggest that the expression of neuronal ABAD depends on estrogen level in the hippocampus and the increase in serum Aβ and hippocampal ABAD induced by ovarian hormone decline may be associated with pre-stage of memory deficit in postmenopausal women and Aβ-mediated AD pathology.

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Section: Discussionsupporting

confidence: 91%

Ovariectomy increases neuronal amyloid-β binding alcohol dehydrogenase level in the mouse hippocampus

Fukuzaki

Takuma

Funatsu

et al. 2008

Neurochemistry International

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“…As in these previous studies, we show here that Aβ, not sAPP, is responsible for synaptic alterations induced by 7PA2-CM. We have not identified the precise form of Aβ responsible for these effects; however, we observed that the effective Aβ concentrations were similar to those typically found in the cerebral spinal fluid of AD patients (Bateman, et al, 2006;Mehta, et al, 2000;Motter, et al, 1995;Pitschke, et al, 1998).…”

Section: Discussionmentioning

confidence: 53%

Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-β protein

Calabrese

Shaked

Tabarean

et al. 2007

Molecular and Cellular Neuroscience

119

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In Alzheimer's disease increasing evidence attributes synaptic and cognitive deficits to soluble oligomers of amyloid β protein (Aβ), even prior to the accumulation of amyloid plaques, neurofibrillary tangles, and neuronal cell death. Here we show that within 1-2 hours picomolar concentrations of cell-derived, soluble Aβ induce specific alterations in pre-and postsynaptic morphology and connectivity in cultured hippocampal neurons. Clusters of presynaptic vesicle markers decreased in size and number at glutamatergic but not GABAergic terminals. Dendritic spines also decreased in number and became dysmorphic, as spine heads collapsed and/or extended long protrusions. Simultaneous time-lapse imaging of axon-dendrite pairs revealed that shrinking spines sometimes became disconnected from their presynaptic varicosity. Concomitantly, miniature synaptic potentials decreased in amplitude and frequency. Spine changes were prevented by blockers of nAChRs and NMDARs. Washout of Aβ within the first day reversed these spine changes. Further, spine changes reversed spontaneously by two days, because neurons acutely developed resistance to continuous Aβ exposure. Thus, rapid Aβ-induced synapse destabilization may underlie transient behavioral impairments in animal models, and early cognitive deficits in Alzheimer's patients.

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“…A moderate to marked decrease in CSF A␤42 in AD to about 50% of control levels has been found using the majority of these methods (Table 1). 35,39,[41][42][43][44][45]47,48 An increase in CSF A␤42 in AD was found in one study. 46 This finding may be attributable to methodological differences (e.g., assay specificity for aggregated or truncated A␤ variants).…”

Section: ␤-Amyloidmentioning

confidence: 88%

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

2004

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Summary:The introduction of acetylcholine esterase (AChE) inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has made patients seek medical advice at an earlier stage of the disease. This has highlighted the importance of diagnostic markers for early AD. However, there is no clinical method to determine which of the patients with mild cognitive impairment (MCI) will progress to AD with dementia, and which have a benign form of MCI without progression. In this paper, the performance of cerebrospinal fluid (CSF) protein biomarkers for AD is reviewed. The diagnostic performance of the three biomarkers, total tau, phospho-tau, and the 42 amino acid form of ␤-amyloid have been evaluated in numerous studies and their ability to identify incipient AD in MCI cases has also been studied. Some candidate AD biomarkers including ubiquitin, neurofilament proteins, growth-associated protein 43 (neuromodulin), and neuronal thread protein (AD7c) show interesting results but have been less extensively studied. It is concluded that CSF biomarkers may have clinical utility in the differentiation between AD and several important differential diagnoses, including normal aging, depression, alcohol dementia, and Parkinson's disease, and also in the identification of Creutzfeldt-Jakob disease in cases with rapidly progressive dementia. Early diagnosis of AD is not only of importance to be able to initiate symptomatic treatment with AChE inhibitors, but will be the basis for initiation of treatment with drugs aimed at slowing down or arresting the degenerative process, such as ␥-secretase inhibitors, if these prove to affect AD pathology and to have a clinical effect.

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Plasma and Cerebrospinal Fluid Levels of Amyloid β Proteins 1-40 and 1-42 in Alzheimer Disease

Abstract: Although mean plasma Abeta40 levels are elevated in sporadic AD and influenced by Apo E genotype, measurement of plasma Abeta40 levels is not useful to support the clinical diagnosis of AD. Lower levels of CSF Abeta42 in the AD group are consistent with previous studies.

Cited by 531 publications

References 37 publications

Ovariectomy increases neuronal amyloid-β binding alcohol dehydrogenase level in the mouse hippocampus

Ovariectomy increases neuronal amyloid-β binding alcohol dehydrogenase level in the mouse hippocampus

Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-β protein

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

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