CSF and serum concentrations of albumin and IgG in Alzheimer's disease

Kay, Arthur D.; May, Conrad; Papadopoulos, Nicholas M.; Costello, Rene; Atack, John; Luxenberg, Jay S.; Cutler, Neal R.; Rapoport, Stanley I.

doi:10.1016/0197-4580(87)90053-4

Cited by 52 publications

(41 citation statements)

References 31 publications

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“…In contrast to the previous studies [3,4,7,[9][10][11] , our study included only AD patients who fulfilled AD criteria [12] and had no significant vascular lesions on MRI. Further, we used not only CDR and MMSE as dementia scales but also MTA on MRI as an indicator of the severity of AD.…”

Section: Discussionmentioning

confidence: 90%

“…Morphological studies of the AD brain revealed abnormalities in the brain microvasculature involving the BBB, which could play a role in the development of AD [2,6] . However, there is little clinical evidence for breakdown of the BBB in AD patients, and the results are still controversial [1,[3][4][5][7][8][9][10][11] , in contrast with cerebral ischemia and vascular dementia, in which clinical abnormalities of BBB are evident [21][22][23] . The albumin ratio did not differ significantly between AD and control cases in some reports [4,7,9] , while it was higher in AD in other reports [3,10,11] .…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have been performed to investigate whether blood-brain barrier (BBB) alterations play a significant role in AD [1][2][3][4][5][6][7][8][9][10][11] . Despite morphological evidence suggesting abnormalities of the brain microvasculature that constitutes the BBB in AD [2] , there is still little clinical evidence supporting BBB disruption in AD patients [1,[3][4][5][7][8][9][10][11] . Understanding of the BBB alteration is important because it may influence the regulation of entry of plasma-derived amyloid-␤ protein (A ␤ ) into the brain as well as the clearance of brain-derived A ␤ .…”

Section: Introductionmentioning

confidence: 99%

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Blood-Brain Barrier Permeability Correlates with Medial Temporal Lobe Atrophy but Not with Amyloid-β Protein Transport across the Blood-Brain Barrier in Alzheimer’s Disease

Matsumoto

Yanase

Noguchi‐Shinohara

et al. 2007

Dement Geriatr Cogn Disord

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Background/Aims: Alterations in the blood-brain barrier (BBB) may play an important role in the pathogenesis and treatment of Alzheimer’s disease (AD). We investigated BBB disturbance and its influence on the equilibrium of amyloid-β protein (Aβ) between plasma and cerebrospinal fluid (CSF) in AD patients. Methods: We analyzed albumin ratio as a marker of the BBB permeability and correlated it with the severity of dementia, brain atrophy on MRI, apolipoprotein E isoform, CSF levels of total tau, CSF and plasma levels of Aβ 1–40 (Aβ₄₀) and 1–42 (Aβ₄₂), and CSF/plasma ratios of Aβ₄₀ and Aβ₄₂ in 42 AD patients. Results: The albumin ratio was positively correlated with the severity of medial temporal lobe atrophy but not with the other parameters including CSF/plasma ratios of Aβ₄₀ or Aβ₄₂. Conclusion: Our results suggest that progression of medial temporal lobe atrophy is associated with increased BBB permeability and that the transport of Aβ across the BBB is not influenced by the BBB alteration in AD.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Blood-Brain Barrier Permeability Correlates with Medial Temporal Lobe Atrophy but Not with Amyloid-β Protein Transport across the Blood-Brain Barrier in Alzheimer’s Disease

Matsumoto

Yanase

Noguchi‐Shinohara

et al. 2007

Dement Geriatr Cogn Disord

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“…Mecocci et al 26 found increased ratios in their multi-infarct dementia patients but not in their AD patients. Kay et al 27 found no increase in the ratio in AD patients nor a correlation between albumin levels in CSF and brain atrophy. Frolich et al 28 also failed to find any differences in the ratio between AD and controls.…”

Section: Disruption Of the Blood-brain Barrier In Alzheimer's Diseasementioning

confidence: 99%

Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease

Erickson

Banks

2013

J Cereb Blood Flow Metab

476

363

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The blood-brain barrier (BBB) plays critical roles in the maintenance of central nervous system (CNS) homeostasis. Dysfunction of the BBB occurs in a number of CNS diseases, including Alzheimer's disease (AD). A prevailing hypothesis in the AD field is the amyloid cascade hypothesis that states that amyloid-b (Ab) deposition in the CNS initiates a cascade of molecular events that cause neurodegeneration, leading to AD onset and progression. In this review, the participation of the BBB in the amyloid cascade and in other mechanisms of AD neurodegeneration will be discussed. We will specifically focus on three aspects of BBB dysfunction: disruption, perturbation of transporters, and secretion of neurotoxic substances by the BBB. We will also discuss the interaction of the BBB with components of the neurovascular unit in relation to AD and the potential contribution of AD risk factors to aspects of BBB dysfunction. From the results discussed herein, we conclude that BBB dysfunction contributes to AD through a number of mechanisms that could be initiated in the presence or absence of Ab pathology. Keywords: Alzheimer's disease; blood-brain barrier; cerebrospinal fluid; diabetes; inflammation; neurovascular unit INTRODUCTION Alzheimer's disease (AD) is the most common type of dementia, and affects B36 million individuals worldwide (http://www.alz. co.uk/research/world-report). The majority of individuals afflicted with AD initially present with symptoms of memory loss and cognitive impairment late in life (Z65 years old). These symptoms increase in severity as AD progresses, often become so debilitating that institutionalization is necessary, and are eventually fatal. Therefore, AD is a disease with tremendous socioeconomic cost. Because of the growing aged population and lack of treatments that can prevent or slow disease progression, future AD prevalence is expected to increase to an extent that it may threaten the sustainability of healthcare systems worldwide. This necessitates a global effort to better understand AD, with the goal of developing treatments that can prevent or slow AD progression. Journal of Cerebral BloodMuch of the focus in AD research has been on amyloid-b peptide (Ab) and tau, which are the protein constituents of the hallmark senile plaques and neurofibrillary tangles that pathologically define AD. The amyloid cascade hypothesis, initially proposed by Hardy and Higgins in 1992, 1 updated by Hardy and Selkoe in 2002, 2 and still a prevalent focus of AD research today, states that deposition of Ab in the brain is the initiating event in AD. Although the hypothesis remains generally accepted, it is also increasingly evident that Ab plays a complex, multifaceted role in AD progression. In rare, familial forms of AD, mutations in the Ab precursor protein (APP) or in presenilin proteins, the enzymes that cleave Ab from APP, cause increased Ab deposition. In the remainder of AD cases, it is thought that Ab deposition results from deficient clearance. 2 Multiple routes of clearance have been elucidat...

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“…As this protein is also expressed [12] and deposited in extracerebral tissues [13], there has been re newed interest in proteins passing the BCB. It has been hypothesized that the entry of precursor proteins from serum into the brain might lead to brain amyloid deposi tion in AD [13], The results from studies on serum and cerebrospinal fluid (CSF) proteins to evaluate BCB func tion are inconsistent [14][15][16][17],…”

mentioning

confidence: 99%

Evidence of Blood-Cerebrospinal Fluid-Barrier Impairment in a Subgroup of Patients with Dementia of the Alzheimer Type and Major Depression: A Possible Indicator for Immunoactivation

Hampel

Müller‐Spahn²,

Berger³

et al. 1995

Dement Geriatr Cogn Disord

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Serum and cerebrospinal fluid (CSF) from 44 patients with clinical probable Alzheimer''s disease (AD) (subdivided in two groups with 18 early onset, EO, and 26 late onset, LO, cases), 10 patients with vascular dementia (VD) and 24 patients with major depression (MD) were assayed for concentrations of albumin and IgG. The severity of dementia was assessed with the Mini Mental State Examination. The CSF/serum ratio for albumin and IgG as well as the IgG index were used to evaluate blood-CSF barrier function. Various patients showed signs of blood-CSF-barrier (BCB) dysfunction and only few displayed evidence of local IgG synthesis in the central nervous system (CNS) in the AD, VD and in the MD group (IgG index >0.7). The permeability of the blood-CSF barrier was not correlated to measures of dementia severity. Our data support the hypothesis of a BCB leakage in a subgroup of all investigated patients. Furthermore, we found a small number of patients with increased intrathecal IgG synthesis. Elevated CSF immunoglobulins combined with BCB impairment might be associated or caused by a general immune activation. Our data are in agreement with the assumption that an inflammatory process may play a role in a subgroup of patients with AD but also with MD and less likely in VD. In conclusion BCB impairment and elevated IgG Immunoglobulin levels are unspeciflc either for AD, VD or MD.

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CSF and serum concentrations of albumin and IgG in Alzheimer's disease

Cited by 52 publications

References 31 publications

Blood-Brain Barrier Permeability Correlates with Medial Temporal Lobe Atrophy but Not with Amyloid-β Protein Transport across the Blood-Brain Barrier in Alzheimer’s Disease

Blood-Brain Barrier Permeability Correlates with Medial Temporal Lobe Atrophy but Not with Amyloid-β Protein Transport across the Blood-Brain Barrier in Alzheimer’s Disease

Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease

Evidence of Blood-Cerebrospinal Fluid-Barrier Impairment in a Subgroup of Patients with Dementia of the Alzheimer Type and Major Depression: A Possible Indicator for Immunoactivation

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