Blunted cerebrovascular response is associated with elevated beta-amyloid

Sisante, Jason-Flor V.; Vidoni, Eric D.; Kirkendoll, Kiersten; Ward, Jaimie L.; Liu, Yumei; Kwapiszeski, Sarah J.; Maletsky, Rebecca; Burns, Jeffrey M.; Billinger, Sandra A.

doi:10.1177/0271678x17732449

Cited by 23 publications

(38 citation statements)

References 40 publications

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“…Another finding of this study was the moderate correlation between BHAI and MMSE. This correlation between CVR and MMSE was consistent with the previous published research …”

Section: Discussionsupporting

confidence: 93%

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Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease

Alwatban

Murman

Bashford

2019

Journal of Neuroimaging

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BACKGROUND AND PURPOSE: A substantial overlap exists between declines in cerebral vasoreactivity (CVR) and symptomatic Alzheimer's disease (AD). CVR can be quantified using transcranial Doppler (TCD) measurement of cerebral blood flow velocities (CBFV) in the middle cerebral artery (MCA) with CO 2 as a vasodilatory stimulus. The breath-hold acceleration index (BHAI) is a new, more reliable measure of CVR developed recently in our laboratory. Our primary goal is to explore the possibility of using TCD for asymptomatic AD screening. METHODS:A pilot study population was divided into three groups: 9 healthy control subjects, 8 subjects identified as preclinical AD, and 10 patients diagnosed with prodromal or mild AD. Control subjects had a Clinical Dementia Rating (CDR) score of 0 without elevated amyloid-β (Aβ) on amyloid positron emission tomography (PET) imaging, preclinical AD subjects had CDR = 0 with elevated Aβ, and prodromal to mild AD subjects had CDR scores ࣙ.5 and elevated Aβ. CVR was calculated using two indices: the conventional breath-holding index (BHI) and the new BHAI. TCD parameters between the three groups were compared. RESULTS: BHAI was able to distinguish between 9 normal control subjects and 8 preclinical-AD subjects with high statistical significance (P < .001). BHI and pulsatility index were able only to distinguish AD from healthy and preclinical subjects (P < .001). CONCLUSIONS: In this exploratory pilot study, CVR was significantly decreased in preclinical, prodromal, and mild AD subjects as compared to the healthy group. Lower CVR in the preclinical AD group was detected using the new BHAI index but not the conventional BHI index.

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“…Another finding of this study was the moderate correlation between BHAI and MMSE. This correlation between CVR and MMSE was consistent with the previous published research …”

Section: Discussionsupporting

confidence: 93%

“…It is interesting that decreased Vd also results from increased intracranial pressure and traumatic brain injury. Many previous TCD studies that examined CBF in AD subjects reported MFV and PI, which can be derived from the flow velocity envelope . However, most do not report Vs and Vd , which are obtained from the velocity envelope signal.…”

Section: Discussionmentioning

confidence: 99%

Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease

Alwatban

Murman

Bashford

2019

Journal of Neuroimaging

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“…When combining these results with the previously reported lower CBF in SAMP8 mice compared to SAMR1 mice (Ding et al, 2019), the results show that the compensatory neurovascular response fails to enhance CBF, demonstrating a cerebral neurovascular dysfunction in SAMP8 mice. One possible reason for this failure is the structural and functional impairments of the cerebral microvasculature, that are induced by Aβ deposition, and which are important mechanisms for AD cerebrovascular damage (Dorr et al, 2012;Kimbrough et al, 2015;Sisante et al, 2019). The cerebral amyloid angiopathy, caused by the deposition of Aβ in the wall of cerebral blood vessels, not only destroys the cerebrovascular structure, but also impairs the neurovascular coupling (Lai et al, 2015;Giannoni et al, 2016;Yan et al, 2017;Hecht et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Benign Regulation of the Astrocytic Phospholipase A2-Arachidonic Acid Pathway: The Underlying Mechanism of the Beneficial Effects of Manual Acupuncture on CBF

et al. 2020

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Background: The astrocytic phospholipase A 2 (PLA 2 )-arachidonic acid (AA) pathway is crucial in understanding the reduction of cerebral blood flow (CBF) prior to cognitive deterioration. In complementary and alternative medicine, manual acupuncture (MA) is used as one of the most important therapies for Alzheimer's disease (AD). The beneficial effects of MA on CBF were reported in our previous study. However, the underlying molecular mechanism remains largely elusive.Objective: To investigate the effect of MA on the astrocytic PLA 2 -AA pathway in SAMP8 mice hippocampi.Methods: SAMP8 mice were divided into the SAMP8 control (Pc) group, the SAMP8 MA (Pm) group and the SAMP8 donepezil (Pd) group. SAMR1 mice were used as the SAMRl control (Rc) group. Mice in the Pd group were treated with donepezil hydrochloride at 0.65 µg/g. In the Pm group, MA was applied at Baihui (GV20) and Yintang (GV29) for 20 min. The above treatments were administered once a day for 26 consecutive days. The Morris water maze was applied to assess spatial learning and memory. Immunofluorescence staining, western blot and liquid chromatographytandem mass spectrometry were used to investigate the expression of related proteins and measure the contents of the metabolic intermediates of the PLA 2 -AA pathway.Results: Compared with that in the Rc group, the escape latency in the Pc group significantly increased (p < 0.01); whereas, the platform crossover number and percentage of time and swimming distance in the platform quadrant decreased (p < 0.01). The hippocampal expression of PLA 2 , cyclooxygenase-1, cytochrome P450 proteins 2C23 and the levels of AA, prostaglandin E 2 and epoxyeicosatrienoic acids of the Pc group was drastically higher than that in the Rc group (p < 0.01). These changes were reversed by MA and donepezil (p < 0.01 or p < 0.05). Frontiers in Neuroscience | www.frontiersin.org February 2020 | Volume 13 | Article 1354 Ding et al. Acupuncture Regulates PLA 2 -AA PathwayConclusion: MA can effectively improve the learning and memory abilities of SAMP8 mice and has a negative regulatory effect on the PLA 2 -AA pathway. We propose that the increase of the arterial tone, which is induced by the inhibition of vasodilatory pathway, may be a reason for the beneficial effect of MA on CBF.Keywords: manual acupuncture, Alzheimer's disease, astrocyte, hippocampus, phospholipase A 2 , arachidonic acid, cerebral blood flow absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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“…Aβ could also lead to blunted cerebrovascular responses . PMVs were reported to participate in Aβ‐induced neurovascular dysfunction through CD36 mediated oxidative stress.…”

Section: Pvm Alterations In Diseased Brainmentioning

confidence: 99%

“…Aβ could also lead to blunted cerebrovascular responses. 71,72 PMVs were reported to participate in Aβ-induced neurovascular and increased number of PVMs in HIVE was observed decades ago. 74 Using simian immunodeficiency virus (SIV)-infected rhesus macaque models, multiples studies reported the existence of SIV RNA and proteins in PVMs but not microglia.…”

Section: Cerebrovascular Diseases and Risk Factorsmentioning

confidence: 99%

Brain perivascular macrophages: Recent advances and implications in health and diseases

2019

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Brain perivascular macrophages (PVMs) belong to a distinct population of brain‐resident myeloid cells located within the perivascular space surrounding arterioles and venules. Their characterization depends on the combination of anatomical localization, phagocytic capacity, and molecular markers. Under physiological status, they provide structural and functional support for maintaining brain homeostasis, including facilitation of blood‐brain barrier integrity and lymphatic drainage, and exertion of immune functions such as phagocytosis and antigen presentation. Increasing evidence also implicates their specific roles in diseased brain, ranging from cerebrovascular diseases, Aβ pathologies, infections, and autoimmunity. Collectively, PVMs are key components of the brain‐resident immune system, actively participate in a broad‐spectrum of processes in normal and diseased status. Details of the processes are largely underexplored. Targeting PVMs would lead to new insights and be a promising strategy for a broad array of human diseases.

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Blunted cerebrovascular response is associated with elevated beta-amyloid

Cited by 23 publications

References 40 publications

Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease

Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease

Benign Regulation of the Astrocytic Phospholipase A2-Arachidonic Acid Pathway: The Underlying Mechanism of the Beneficial Effects of Manual Acupuncture on CBF

Brain perivascular macrophages: Recent advances and implications in health and diseases

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