Cerebral ABC Transporter-common Mechanisms May Modulate Neurodegenerative Diseases and Depression in Elderly Subjects

Pahnke, Jens; Fröhlich, Christina; Paarmann, Kristin; Krohn, Markus; Bogdanović, Nenad; Årsland, Dag; Winblad, Bengt

doi:10.1016/j.arcmed.2014.10.010

Cited by 29 publications

(15 citation statements)

References 73 publications

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“… 69–72 Possession of ApoE ε4 and ageing impact adversely on all these molecular and cellular clearance mechanisms, as well as on ATP-binding cassette transporters involved in the clearance of Aβ. 73–75 …”

Section: The Pathophysiology Of Vascular Aβ Deposition: An Updatementioning

confidence: 99%

The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice

Banerjee

Carare

Cordonnier

et al. 2017

J Neurol Neurosurg Psychiatry

178

137

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Cerebral amyloid angiopathy (CAA) has never been more relevant. The last 5 years have seen a rapid increase in publications and research in the field, with the development of new biomarkers for the disease, thanks to advances in MRI, amyloid positron emission tomography and cerebrospinal fluid biomarker analysis. The inadvertent development of CAA-like pathology in patients treated with amyloid-beta immunotherapy for Alzheimer’s disease has highlighted the importance of establishing how and why CAA develops; without this information, the use of these treatments may be unnecessarily restricted. Our understanding of the clinical and radiological spectrum of CAA has continued to evolve, and there are new insights into the independent impact that CAA has on cognition in the context of ageing and intracerebral haemorrhage, as well as in Alzheimer’s and other dementias. While the association between CAA and lobar intracerebral haemorrhage (with its high recurrence risk) is now well recognised, a number of management dilemmas remain, particularly when considering the use of antithrombotics, anticoagulants and statins. The Boston criteria for CAA, in use in one form or another for the last 20 years, are now being reviewed to reflect these new wide-ranging clinical and radiological findings. This review aims to provide a 5-year update on these recent advances, as well as a look towards future directions for CAA research and clinical practice.

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Section: The Pathophysiology Of Vascular Aβ Deposition: An Updatementioning

confidence: 99%

The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice

Banerjee

Carare

Cordonnier

et al. 2017

J Neurol Neurosurg Psychiatry

178

137

View full text Add to dashboard Cite

show abstract

“…These oligomers disrupt a variety of receptors [2], increase membrane permeability [2] and are suspected to induce hyperphosphorylation and aggregation of tau [3]. Physiologically, Aβ is largely eliminated from the brain by LRP1 [4] and several ABC transporters (reviewed in [5, 6]). The vast majority of cases occur sporadically and a large series of risk factors have been identified, including age, type 2 diabetes, high blood pressure, and various genetic factors like specific alleles of apolipoprotein E (APOE) [7, 8].…”

Section: Introductionmentioning

confidence: 99%

Revisiting rodent models: Octodon degus as Alzheimer’s disease model?

Steffen

Krohn

Paarmann

et al. 2016

acta neuropathol commun

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Alzheimer’s disease primarily occurs as sporadic disease and is accompanied with vast socio-economic problems. The mandatory basic research relies on robust and reliable disease models to overcome increasing incidence and emerging social challenges. Rodent models are most efficient, versatile, and predominantly used in research. However, only highly artificial and mostly genetically modified models are available. As these ‘engineered’ models reproduce only isolated features, researchers demand more suitable models of sporadic neurodegenerative diseases. One very promising animal model was the South American rodent Octodon degus, which was repeatedly described as natural ‘sporadic Alzheimer’s disease model’ with ‘Alzheimer’s disease-like neuropathology’. To unveil advantages over the ‘artificial’ mouse models, we re-evaluated the age-dependent, neurohistological changes in young and aged Octodon degus (1 to 5-years-old) bred in a wild-type colony in Germany. In our hands, extensive neuropathological analyses of young and aged animals revealed normal age-related cortical changes without obvious signs for extensive degeneration as seen in patients with dementia. Neither significant neuronal loss nor enhanced microglial activation were observed in aged animals. Silver impregnation methods, conventional, and immunohistological stains as well as biochemical fractionations revealed neither amyloid accumulation nor tangle formation. Phosphoepitope-specific antibodies against tau species displayed similar intraneuronal reactivity in both, young and aged Octodon degus.In contrast to previous results, our study suggests that Octodon degus born and bred in captivity do not inevitably develop cortical amyloidosis, tangle formation or neuronal loss as seen in Alzheimer’s disease patients or transgenic disease models.

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“…ABCA7. ABCA7 exports phospholipids and cholesterol across cell membranes and binds to apolipoproteins such as ApoE (110). ABCA7 was shown to be a susceptibility locus to late-onset AD (116)(117)(118)(119)(120).…”

Section: Atp-binding Cassette Transportersmentioning

confidence: 99%

“…ABCA2, similar to ABCA1, is related to cholesterol homeostasis, through the regulation of the low‐density lipoprotein receptor expression. In addition, it facilitates the trafficking of cholesterol from endosomes to the endoplasmic reticulum, the site for Aβ generation . ABCA2 has been genetically related to AD .…”

Section: Role Of Sex Hormones In the Control Of Aβ Levels In The Brainmentioning

confidence: 99%

Sex Hormone Decline and Amyloid β Synthesis, Transport and Clearance in the Brain

Duarte

Hrynchak

Gonçalves

et al. 2016

J Neuroendocrinology

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Sex hormones (SH) are essential regulators of the central nervous system. The decline in SH levels along with ageing may contribute to compromised neuroprotection and set the grounds for neurodegeneration and cognitive impairments. In Alzheimer's disease, besides other pathological features, there is an imbalance between amyloid b (Ab) production and clearance, leading to its accumulation in the brain of older subjects. Ab accumulation is a primary cause for brain inflammation and degeneration, as well as concomitant cognitive decline. There is mounting evidence that SH modulate Ab production, transport and clearance. Importantly, SH regulate most of the molecules involved in the amyloidogenic pathway, their transport across brain barriers for elimination, and their degradation in the brain interstitial fluid. This review brings together data on the regulation of Ab production, metabolism, degradation and clearance by SH.

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Cerebral ABC Transporter-common Mechanisms May Modulate Neurodegenerative Diseases and Depression in Elderly Subjects

Cited by 29 publications

References 73 publications

The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice

The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice

Revisiting rodent models: Octodon degus as Alzheimer’s disease model?

Sex Hormone Decline and Amyloid β Synthesis, Transport and Clearance in the Brain

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