Amyloid β protein 1–40 and 1–42 levels in matched cerebrospinal fluid and plasma from patients with Alzheimer disease

Mehta, Pankaj; Pirttilä, Tuula; Patrick, Bruce A.; Barshatzky, Marc; Mehta, Sangita P.

doi:10.1016/s0304-3940(01)01754-2

Cited by 230 publications

(173 citation statements)

References 20 publications

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…Second, levels of Aβ in the central pool are higher than those in the peripheral pool. Concentrations of Aβ in cerebrospinal fluid (CSF) are at least 5-15 times higher than those in plasma 7,8 . One possible interpretation is that APP processing in peripheral cells probably occurs via α-cleavage (rather than the β-cleavage used in neurons) 9,10 , resulting in decreased peripheral production of Aβ.…”

mentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

View full text Add to dashboard Cite

The global burden of Alzheimer disease (AD), already the most common type of dementia, is expected to increase still further owing to population ageing. AD not only causes severe distress for patients and caregivers, but also results in a large economic burden on society. Current major challenges in AD include the lack of reliable biomarkers for its early diagnosis, as well as the lack of effective preventive strategies and treatments 1,2 . Thus, increased understanding of the molecular patho genesis of AD could lead to the development of improved diagnostic and therapeutic strategies.AD is conventionally regarded as a CNS disorder. However, increasing experimental, epidemiological and clinical evidence has suggested that manifestations of AD extend beyond the brain. These systemic alterations might not be simply secondary effects of the cerebral degeneration seen in AD, but could reflect under lying processes linked to progression of the disease. AD pathogenesis is complex, involving abnormal amyloid-β (Aβ) metabolism, tau hyperphosphorylation, oxidative stress, reactive glial and microglial changes, and other pathological events. Given that Aβ is a major hallmark of AD and a fertile area of research in this disease, this Review focuses on the systemic role of Aβ in AD. We discuss the communication between peripheral and central pools of Aβ, and describe interactions between systemic abnormalities and AD pathogenesis in the brain. We review emerging findings of associations between systemic abnormalities and Aβ metabolism, and describe how these associations might interact with or reflect on the central pathways of Aβ production and clearance. On the basis of these findings, we suggest that interactions between the brain and the periphery might have a crucial role in the development and progression of AD. Aβ biogenesis and catabolismA steady accrual of data from laboratories and clinics is providing increasing support for the concept that an imbalance between the production and clearance of Aβ is a very early (and often initiating) factor in AD 3 . Normal metabolism of Aβ and maintenance of the homeostatic balance between Aβ production and clearance is, therefore, essential to maintain brain health. In fact, physiological metabolism of Aβ occurs not only in the brain but also in the periphery, and communication between these regions is possible (FIG. 1). Central and peripheral production of AβAβ is derived from the proteolytic cleavage of amyloid precursor protein (APP), which is expressed not only in brain cells, including neurons, astrocytes and microglia, but also in peripheral organs and tissues, such as the Abstract | Alzheimer disease (AD) is the most common type of dementia, and is currently incurable; existing treatments for AD produce only a modest amelioration of symptoms. Research into this disease has conventionally focused on the CNS. However, several peripheral and systemic abnormalities are now understood to be linked to AD, and our understanding of how these alterations contribute to AD is becom...

show abstract

mentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Further, extracerebral production of A4b2 by platelets may contribute to increase of plasma Ab42. 41 TBI is a pleotropic condition with multiple mechanisms of secondary injury and recovery. As a result, a single biomarker is unlikely to reflect the extent and diversity of neural tissue damage, aid in monitoring mechanism-directed therapies, or reliably forecast outcomes.…”

Section: Discussionmentioning

confidence: 99%

Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury

Bogoslovsky

Wilson

Yao

et al. 2017

Journal of Neurotrauma

174

126

View full text Add to dashboard Cite

Glial fibrillary acidic protein (GFAP), microtubule-associated protein tau, and amyloid b peptide (Ab42) have been proposed as diagnostic and prognostic biomarkers in traumatic brain injury (TBI). Single molecule array (Simoa) is a novel technology that employs highly sensitive immunoassays for accurate measurements of candidate biomarkers found at low concentration in biological fluids. Our objective was to trace the trajectory of tau, GFAP, and Ab42 levels in plasma from the acute through subacute stages after TBI, compared with controls. Samples from 34 TBI subjects enrolled in the Citicoline Brain Injury Treatment Trial (COBRIT) were studied. Injury severity was assessed by Glasgow Coma Scale (GCS) and admission CT. Glasgow Outcome Scale Extended (GOSE) was assessed 6 months after injury. Plasma was collected within 24 h (Day 0), and 30 and 90 days after the TBI. Plasma collected from 69 healthy volunteers was used for comparison. At every time point, increases were noted in plasma GFAP ( p < 0.0001 for all comparisons), tau ( p < 0.0001, p < 0.0001, and p = 0.0044, at Days 0, 30, and 90, respectively), and Ab42 ( p < 0.001, p < 0.0001, and p = 0.0203, respectively) in TBI cases compared with controls. The levels were maximal at Day 0 for GFAP and tau and at Day 30 for Ab42. Area under curve (AUC) analyses for Day 0 GFAP and tau were excellent for discrimination of complicated mild TBI (cmTBI) from controls (0.936 and 0.901, correspondingly). Discriminant component analysis (DCA) for all three biomarkers at Days 0 and 30 differentiated controls from cmTBI (91.1% and 89.7% correctly classified, at each time point). Duration of post-traumatic amnesia (PTA) correlated weakly with tau levels at 30 days (Spearman's r = 0.40; 95% CI 0.0003-0.60, p = 0.044). The Marshall CT Grade on admission correlated weakly with Day 30 tau levels (Spearman's r = 0.41; 95% CI 0.04-0.68, p = 0.027). Day 30 Ab42 correlated with GOSE (standardized b -0.486, p = 0.042). GFAP, tau and Ab42 were increased up to 90 days after TBI compared with controls. Total tau levels correlated with clinical and radiological variables of TBI severity. Plasma Ab42 correlated with clinical outcome. Combination of all three biomarkers at Days 0 and 30 can be used to differentiate controls from cmTBI populations, and may be useful as biomarkers of TBI in both acute and subacute phases.

show abstract

“…Studies have suggested that high plasma Aβ levels are a risk factor for developing AD. 22,24,25 In one of the studies, plasma Aβ42 declined more rapidly over three years in individuals who developed AD. 21 In other studies, no correlation between plasma Aβ levels and disease progression or severity was observed.…”

Section: Blood Biomarkers For Alzheimer's Disease Blood Biomarkers Fomentioning

confidence: 99%

Blood Biomarkers for Alzheimer’s Disease

Winblad¹,

Lönneborg²

2008

European Neurological Review

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a multifactorial and heterogeneous disease in both its clinical and histopathological appearance. In more than 99% of cases the cause of the disease is not understood. Independent of its cause, AD is clinically characterised by a developing dementia and histopathologically characterised by neuronal degeneration.Although the presence of neurofibrillary tangles (NFTs) and neurotic The development of biomarkers for AD is challenging as it is complicated by several factors. In addition to the variability in clinical features and multiple molecular aetiologies, the development of AD biomarkers is burdened with a diagnostic imprecision as confirmation of the disease preferentially has to await a post mortem histopathological examination.The long asymptomatic prodromal stages, rates of progression and complex disease genetics complicate the situation further. In this article we will review the current developments in the field of biomarkers for the detection of AD in blood. Single-component BiomarkersThe physiology of the blood-brain barrier limits potential biomarkers that are closely associated to brain pathophysiology to small molecules, lipophilic molecules and molecules with specific transporters. 12 Brainderived proteins and metabolites that pass into the plasma will also become markedly diluted in a biochemically complex medium. 12 Moreover, it is not known whether there are any direct pathophysiological processes associated with AD in blood cells. The traditional approach of using one or a few closely related molecules as a biomarker, a single-component biomarker, in plasma, serum or blood has been utilised since the late 1990s. [13][14][15] However, their usefulness has been limited, mainly due to discrepant results between studies. Amyloid β-proteinAβ can be detected in plasma and is thus a compelling candidate biomarker for AD. The plasma total Aβ or Aβ42 was increased in familial AD with presenilin or APP mutations 16,17 and in Down's syndrome with APP triplication, 18 which raises the possibility that sporadic AD may also be associated with detectable and diagnostic changes in Aβ plasma levels. Animal models suggest that Aβ can pass between cerebrospinal fluid (CSF) and plasma compartments, 19,20 but this has yet to be confirmed in humans. APP is also produced by platelets and is, therefore, an alternative source for the APP and Aβ pools found in plasma.

show abstract

Amyloid β protein 1–40 and 1–42 levels in matched cerebrospinal fluid and plasma from patients with Alzheimer disease

Cited by 230 publications

References 20 publications

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury

Blood Biomarkers for Alzheimer’s Disease

Contact Info

Product

Resources

About