The overlap between vascular disease and Alzheimer’s disease - lessons from pathology

Attems, Johannes; Jellinger, K. A.

doi:10.1186/s12916-014-0206-2

Cited by 569 publications

(467 citation statements)

References 193 publications

(217 reference statements)

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“…Accumulation of Ab within cerebral vessel walls, known as CAA, is a common pathological feature in AD (Attems and Jellinger, 2014). To determine if CAA can form in our bioengineered vascular model, we injected monomeric Ab40 or Ab42 on the anteluminal side of the vessel to mimic native conditions where Ab is predominantly produced by neurons.…”

Section: Monomeric Ab Accumulates and Aggregates In Bioengineered Bipmentioning

confidence: 99%

“…In addition to AD's neuropathological hallmarks of amyloid plaques consisting of deposited Ab peptides and neurofibrillary tangles consisting of hyperphosphorylated tau proteins, 60-90% of AD brains have evidence of cerebral amyloid angiopathy (CAA), cerebral small vessel disease and microvascular degeneration (Attems and Jellinger, 2014). Apolipoprotein (apo) E, which in the brain is secreted primarily from astrocytes, is the principal lipid carrier within the central nervous system (CNS) and, in humans, exists as three isoforms, namely APOE2, APOE3, and APOE4 (Lane- Donovan and Herz, 2017).…”

Section: Introductionmentioning

confidence: 99%

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[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Robert

Button

Soo

et al. 2017

Alzheimer's & Dementia

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Amyloid plaques, consisting of deposited beta-amyloid (Ab), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, as Ab is cleared from the brain by pathways involving the cerebrovasculature, most AD patients have cerebrovascular amyloid (cerebral amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. Here we present a notable advance in vascular tissue engineering by generating the first functional 3-dimensioinal model of CAA in bioengineered human vessels. We show that lipoproteins including brain (apoE) and circulating (high-density lipoprotein, HDL) synergize to facilitate Ab transport across bioengineered human cerebral vessels. These lipoproteins facilitate Ab42 transport more efficiently than Ab40, consistent with Ab40 being the primary species that accumulates in CAA. Moreover, apoE4 is less effective than apoE2 in promoting Ab transport, also consistent with the well-established role of apoE4 in Ab deposition in AD.

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Section: Monomeric Ab Accumulates and Aggregates In Bioengineered Bipmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Robert

Button

Soo

et al. 2017

Alzheimer's & Dementia

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“…Although there is an established relationship between vascular and degenerative (AD) pathology, the mechanistic links between the two have to be identifi ed. In general, however, vascular brain damage is believed to be an important component of AD pathophysiology [24]. Just one example: Analysis of 4629 cases of the NACC database with autopsy-confi rmed AD classifi ed 79.7% as having additional CVD [25].…”

Section: Clinical Featuresmentioning

confidence: 99%

“…Due to frequent co-morbidity in old age, cerebrovascular pathology often coexists with Alzheimer-type lesions and other pathologies. 25 to over 80% (mean 75%) of elderly both demented and non-demented individuals show mixed pathologies [21,24,42]. …”

Section: Pathogenesis Of Cvi/vadmentioning

confidence: 99%

“…Although there is a frequent overlap between vascular and degenerative lesions causing cognitive impairment [17,24], and a frequent lack of correlations between clinical and pathology fi ndings [26], there is a consistent interplay of pathogenic factors causing VCI (Figure 2). Due to frequent co-morbidity in old age, cerebrovascular pathology often coexists with Alzheimer-type lesions and other pathologies.…”

Section: Pathogenesis Of Cvi/vadmentioning

confidence: 99%

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Current Pathogenetic Concepts of Vascular Cognitive Impairment

Jellinger¹

2016

J Neurol Neurol Sci Disord

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The term vascular cognitive impairment designates a heterogenous group of disorders ranging from mild cognitive impairment to full-blown dementia -vascular dementia -resulting from cerebrovascular lesions involving various brain areas. Current clinical criteria show moderate sensitivity (50-56%) and variable specifi city (range 64-98%). The prevalence in autopsy series ranges from 0.03 to 58% (mean 8-15% in Western series, 22-35% in Japan). Major morphological types -multi-infarct and subcortical vascular encephalopathy, strategic infarct dementia, lacunar state, cortical granular atrophy (rare), and ischemic encephalopathy -are caused by atherosclerosis of major cerebral arteries and small vessel disease, resulting from systemic, cardiac and local vascular disease or cerebral amyloid angiopathy. Pathogenesis of vascular dementia is multifactorial, and pathophysiology affects brain areas and neurological networks involved in cognition, memory, behavior, and executive functions. Vascular brain injury in elderly persons often coexists with Alzheimer-type lesions and other pathologies resulting in mixed dementia. However, these lesions are also present in many non-demented elderly subjects. The heterogeneity of clinical manifestations, cerebrovascular pathology and their pathogenic factors result in limitations of the accuracy of diagnostic criteria for vascular dementia. Therefore, standardized and reproducible neuropathological criteria for the assessment of cerebrovascular lesions associated with cognitive impairment in order to elucidate contribution of cerebrovascular disease to cognitive impairment are urgently needed.

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Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions

Nasrallah

Pajewski

Auchus

et al. 2019

JAMA

312

228

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The effect of intensive blood pressure lowering on brain health remains uncertain. OBJECTIVE To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes. DESIGN, SETTING, AND PARTICIPANTS A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016. INTERVENTIONS Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315). MAIN OUTCOMES AND MEASURES The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome. RESULTS Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm 3 (difference, 0.92 cm 3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm 3 (difference, 1.45 cm 3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, −0.54 cm 3 [95% CI, −0.87 to −0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm 3 (difference, −30.6 cm 3 [95% CI, −32.3 to −28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm 3 (difference, −26.9 cm 3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, −3.7 cm 3 [95% CI, −6.3 to −1.1]). CONCLUSIONS AND RELEVANCE Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small.

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The overlap between vascular disease and Alzheimer’s disease - lessons from pathology

Cited by 569 publications

References 193 publications

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

[O2–04–01]: Clearance of Beta‐amyloid Is Facilitated by Apolipoprotein E and Circulating High‐density Lipoproteins in Bioengineered Human Vessels

Current Pathogenetic Concepts of Vascular Cognitive Impairment

Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions

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