Fate of Cerebrospinal Fluid‐Borne Amyloid β‐Peptide: Rapid Clearance into Blood and Appreciable Accumulation by Cerebral Arteries

Ghersi‐Egea, Jean‐François; Gorevic, Peter D.; Ghiso, Jorge; Frangione, Blas; Patlak, Clifford S.; Fenstermacher, Joseph D.

doi:10.1046/j.1471-4159.1996.67020880.x

Cited by 226 publications

(155 citation statements)

References 10 publications

Supporting

Mentioning

142

Contrasting

Order By: Relevance

“…In addition, animal experiments have shown that, after intracranial or intravenous infusion of 125 I-labelled Aβ, radioactivity is subsequently detected in the kidney and urine 23,110 . These findings indicate that the kidney might participate in physiological clearance of Aβ by filtering Aβ from blood to urine.…”

Section: Renal Dysfunctionmentioning

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

Section: Renal Dysfunctionmentioning

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

“…18 While an exact pathophysiological link between AD and NPH is not known, one explanation might rest on altered CSF dynamics resulting in pathologic accumulation of β-amyloid in the brain. 6,20 Investigators have also noted that NPH as a single entity may be quite rare and that an AD-NPH syndrome may manifest as a result of coexisting NPH and AD pathology. 4,15,20 Idiopathic NPH seems to involve an underlying pathophysiology wide in scope, one that ranges from hemodynamic disturbance to major cerebral parenchymal changes.…”

Section: Discussionmentioning

confidence: 99%

Concurrent Alzheimer’s pathology in patients with clinical normal pressure hydrocephalus: correlation of high-volume lumbar puncture results, cortical brain biopsies, and outcomes

Pomeraniec¹,

Bond²,

Lopes

et al. 2016

JNS

View full text Add to dashboard Cite

abbreviatioNs AD = Alzheimer's disease; CERAD = Consortium to Establish a Registry for Alzheimer's Disease; CSF = cerebrospinal fluid; GDS = Global Deterioration Scale; HVLP = high-volume lumbar puncture; NPH = normal pressure hydrocephalus. obJective Normal pressure hydrocephalus (NPH) remains most often a clinical diagnosis and has been widely considered responsive to the placement of a cerebrospinal fluid (CSF) shunt. The high incidence of patients with Alzheimer's disease (AD) with NPH symptoms leads to poorer outcomes than would be expected in patients with NPH alone. This article reviews a series of patients operated on for presumed NPH in whom preoperative high-volume lumbar puncture (HVLP) and intraoperative cortical brain biopsies were performed. The data derived from these procedures were then used to understand the incidence of AD in patients presenting with NPH symptoms and to analyze the efficacy of HVLP in patients with NPH and patients with concurrent AD (NPH+AD). A review of the outcomes of shunt surgery is provided. methods The cases of all patients who underwent placement of a CSF shunt for NPH from 1998 to 2013 at the University of Virginia by the senior author were retrospectively reviewed. Patients who underwent HVLP and patients who underwent cortical brain biopsies were stratified based on the biopsy results into an NPH-only group and an NPH+AD group. The HVLP results and outcomes were then compared in these 2 groups. results From 1998 to 2013, 142 patients underwent shunt operations because of a preoperative clinical diagnosis of NPH. Of the patients with a shunt who had a diagnosis of NPH, 105 (74%) received HVLPs. Of 142 shunt-treated patients with NPH, 27 (19%) were determined to have concomitant Alzheimer's pathology based on histopathological findings at the time of shunting. Patients who underwent repeat biopsies had an initial positive outcome. After they clinically deteriorated, they underwent repeat biopsies during shunt interrogation, and 13% of the repeat biopsies demonstrated Alzheimer's pathology. Improvements in gait and cognition did not reach significance between the NPH and NPH+AD groups. In total, 105 patients underwent HVLP before shunt placement. In the NPH cohort, 44.6% of patients experienced improvement in symptoms with HVLP and went on to experience resolution or improvement. In the NPH+AD cohort, this proportion was lower (18.2%), and the majority of patients who experienced symptomatic relief with HVLP actually went on to experience either no change or worsening of symptoms (p = 0.0136). coNclusioNs A high prevalence of AD histopathological findings (19%) occurred in patients treated with shunts for NPH based on cortical brain biopsies performed during placement of CSF shunts. HVLP results alone were not predictive of clinical outcome. However, cortical brain biopsy results and the presence of Alzheimer's pathology had a strong correlation with success after CSF shunting. Thirteen percent of patients who initially had a normal cortical brain biopsy result had evi...

show abstract

“…An alteration of choroid plexus vascular and epithelial morphology, a decrease in choroidal synthesis and transport capacity, and a decrease in CSF secretion is observed in aging, and is exacerbated in Alzheimer's disease [132,134]. The CSF circulation plays a role in amyloid beta distribution and clearance from the brain [49]. An impaired drainage of the brain induced by a decreased CSF secretion may, therefore, favor amyloid deposition.…”

Section: Csf Secretionmentioning

confidence: 99%

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

et al. 2018

View full text Add to dashboard Cite

The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.

show abstract

Fate of Cerebrospinal Fluid‐Borne Amyloid β‐Peptide: Rapid Clearance into Blood and Appreciable Accumulation by Cerebral Arteries

Cited by 226 publications

References 10 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

Concurrent Alzheimer’s pathology in patients with clinical normal pressure hydrocephalus: correlation of high-volume lumbar puncture results, cortical brain biopsies, and outcomes

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

Contact Info

Product

Resources

About