Jurre den Haan

Retinal thickness in Alzheimer's disease: A systematic review and meta-analysis

Retinal characteristics are increasingly recognized as biomarkers for neurodegenerative diseases. Retinal thickness measured by optical coherence tomography may reflect the presence of Alzheimers disease (AD). We performed a meta‐analysis on retinal thickness in AD and mild cognitive impairment (MCI) patients and healthy controls (HCs).

Retinal thickness correlates with parietal cortical atrophy in early-onset Alzheimer's disease and controls

The retina may reflect Alzheimers disease (AD) neuropathological changes and is easily visualized with optical coherence tomography (OCT). Retinal thickness decrease has been correlated to AD, however, without information on amyloid status. We correlated retinal (layer) thickness to AD biomarkers in amyloid‐positive early‐onset AD (EOAD) patients and amyloid‐negative controls.Introduction The retina may reflect Alzheimers disease (AD) neuropathological changes and is easily visualized with optical coherence tomography. Retinal thickness decrease has been correlated to AD, however, without information on amyloid status. We correlated retinal (layer) thickness to AD biomarkers in amyloid-positive early-onset AD (EOAD) patients and amyloid-negative controls.

NEUROPATHOLOGICAL HALLMARKS OF ALZHEIMER’S DISEASE IN POSTMORTEM AD RETINAS

Figure 1. Proc PFA and dissec ridian. Section staining is show tinal nerve fib layer, INL1⁄4in nuclear layer, Jurre den Haan, Tjado H. J. Morrema, Jacoline B. ten Brink, Frank Verbraak, Johannes de Boer, Philip Scheltens, Annemieke M. Rozemuller, Arthur A. B. Bergen, Femke H. Bouwman, Jeroen J. M. Hoozemans, Neuroscience Campus Amsterdam, Netherlands, Amsterdam, Netherlands; Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, Netherlands; VU University Medical Center, Department of Pathology, Amsterdam Neuroscience, Amsterdam, Netherlands; Department of Ophthalmogenetics, Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; OphthalmologyDepartment VUUniversityMedical Center, Amsterdam, Netherlands; Department of Physics, VU University, BioLaserLab, Amsterdam, Netherlands; VU University Medical Center, Amsterdam, Netherlands; Alzheimer Center and Department of Neurology, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, Netherlands; VU University Medical Center, Amsterdam Neuroscience, Amsterdam, Netherlands. Contact e-mail: j.denhaan1@vumc.nl

Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnostics

The combined fluorescent and Aβ-binding properties of the dietary spice curcumin could yield diagnostic purpose in the search for a non-invasive Aβ-biomarker for Alzheimer’s disease (AD). However, evidence on the binding properties of curcumin, its conjugates and clinically used bio-available formulations to AD neuropathological hallmarks is scarce. We therefore assessed the binding properties of different curcumin forms to different neuropathological deposits in post-mortem brain tissue of cases with AD, other neurodegenerative diseases, and controls. Post mortem brain tissue was histochemically assessed for the binding of curcumin, its isoforms, conjugates and bio-available forms and compared to routinely used staining methods. For this study we included brains of early onset AD, late onset AD, primary age-related tauopathy (PART), cerebral amyloid angiopathy (CAA), frontotemporal lobar degeneration (FTLD) with tau or TAR DNA-binding protein 43 (TDP-43) inclusions, dementia with Lewy bodies (DLB), Parkinson’s disease (PD) and control cases without brain pathology. We found that curcumin binds to fibrillar amyloid beta (Aβ) in plaques and CAA. It does not specifically bind to inclusions of protein aggregates in FTLD-tau cases, TDP-43, or Lewy bodies. Curcumin isoforms, conjugates and bio-available forms show affinity for the same Aβ structures. Curcumin staining overlaps with immunohistochemical detection of Aβ in fibrillar plaques and CAA, and to a lesser extent cored plaques. A weak staining of neurofibrillary tangles was observed, while other structures immunopositive for phosphorylated tau remained negative. In conclusion, curcumin, its isoforms, conjugates and bio-available forms selectively bind fibrillar Aβ in plaques and CAA in post mortem AD brain tissue. Curcumin, being a food additive with fluorescent properties, is therefore an interesting candidate for in-vivo diagnostics in AD, for example in retinal fluorescent imaging.

Ganglion cell layer measurements correlate with disease severity in patients with Alzheimer's disease

1979). Today, using OCTA, it is possible to study the complex vascular anatomical architecture of the DCP in DR, which might be more susceptible to diabetic damage because of its complexity. In a previous study using OCTA (Simonett et al. 2017), we found that DM1 patients with no and mild signs of non-proliferative DR showed a reduction in DCP parafoveal vessel density. In this study, by analysing a subgroupof DM1 patients, we demonstrated that patientswith no signs ofDRalso present DCP microvascular impairment. Local retinal acidosis, found in the outer nuclear layer at the early stages of a DR(Dmitriev et al. 2016), could increase leucostasis in small retinal capillaries. Also, diabetic maculopathy seems to be a result of disturbances in retinal vasomotion. (Bek 1999) Therefore, our findings might corroborate the hypothesis that the increased recruitment of microvascular units in the macular area can lead to increased hydrostatic pressure in small capillaries (Bek 1999) with a consequent severely diminished blood flow velocity/rate below the threshold necessary to register as flow in the OCTA system. Finally, the diabetic metabolic disturbances, particularly changes in blood glucose, can influence retinal perfusion and retinal autoregulation, implying that fluctuations in the arterial feeding pressure may be transmitted to the smaller vessels. Limitations are the small sample size and a limited field of view of 3 9 3 mm area. Additionally, we cannot exclude that projection from more superficial vasculature may be affecting these findings, particularly in the DCP, for either DM1 patients or control. (Shahlaee et al. 2016) In conclusion,DCP impairmentmight be harbinger of retinal vascular damage before any sign of DR can be detected by means of ophthalmoscopy, and this finding demonstrated that a decrease in DCP parafoveal capillary density represents an early process in the disease.

AMYLOID VISUALIZATION IN THE RETINA OF ALZHEIMER’S DISEASE PATIENTS WITH CURCUMIN

was a significant relationship between the number of retinal microhemorrhages and Fazekas ratings for WMH in the CAA patients (r1⁄4.853, p<.01), and this trended towards significance when examining the area of retinal micro-hemorrhages (r1⁄4.615, p1⁄4.078). Finally, there was a relationship between area (r1⁄4-.695, p<.05) and number (r1⁄4-.573, p1⁄4.107) of retinal micro-hemorrhages and performance on measures of episodic memory in the CAA group. Conclusions:There were significantly more retinal micro-hemorrhages in a group of CAA patients than a group of healthy controls, and this relationship was moderated by blood pressure. The strong association between retinal micro-hemorrhages and cerebral WMH parallels literature indicating a progressive increase in cerebral WMH with lobar hemorrhages in CAA (Chen et al., 2006). The relationship between retinal micro-hemorrhages, cerebral WMH, and cognitive performance warrants further exploration in larger samples using longitudinal design, and retinal micro-hemorrhages merit further exploration as a potential biomarker of CAA.

RETINAL THICKNESS CORRELATES WITH PARIETAL CORTICAL ATROPHY ON MRI

CI, 0.73-0.83)], [Ab1-42+NFL] differentiating MCI from ADD [AUROC1⁄40.71 (95% CI, 0.67-0.75)], and t-tau differentiating ADD from FTD [AUROC1⁄40.82 (95% CI, 0.78-0.86). Conclusions: The biomarker combination [Ab1-42+p-tau+NFL] differentiated ADD from HC with good diagnostic accuracy. CSFAb1-42 discriminated MCI from HC with poor diagnostic accuracy. The diagnostic performances of CSF t-tau in distinguishing FTD fromHC and ADD were fair and good, respectively. The combination [Ab1-42+NFL] differentiatedMCI fromADDwith fair diagnostic accuracy. In summary, NFL protein – combined with the core AD biomarkers Ab1-42 and p-tau – is a novel pathophysiological biomarker potentially contributing to improving the diagnostic accuracy in differentiating ADD from HC and, to a lesser degree, ADD from MCI.

Retinal thickness correlates with parietal cortical atrophy in EOAD and controls

The retina may reflect Alzheimers disease (AD) neuropathological changes and is easily visualized with optical coherence tomography (OCT). Retinal thickness decrease has been correlated to AD, however, without information on amyloid status. We correlated retinal (layer) thickness to AD biomarkers in amyloid‐positive early‐onset AD (EOAD) patients and amyloid‐negative controls.Introduction The retina may reflect Alzheimers disease (AD) neuropathological changes and is easily visualized with optical coherence tomography. Retinal thickness decrease has been correlated to AD, however, without information on amyloid status. We correlated retinal (layer) thickness to AD biomarkers in amyloid-positive early-onset AD (EOAD) patients and amyloid-negative controls.

Retinal Imaging BiomarkersRetinal thickness correlates with parietal cortical atrophy in EOAD and controls

The retina may reflect Alzheimers disease (AD) neuropathological changes and is easily visualized with optical coherence tomography (OCT). Retinal thickness decrease has been correlated to AD, however, without information on amyloid status. We correlated retinal (layer) thickness to AD biomarkers in amyloid‐positive early‐onset AD (EOAD) patients and amyloid‐negative controls.Introduction The retina may reflect Alzheimers disease (AD) neuropathological changes and is easily visualized with optical coherence tomography. Retinal thickness decrease has been correlated to AD, however, without information on amyloid status. We correlated retinal (layer) thickness to AD biomarkers in amyloid-positive early-onset AD (EOAD) patients and amyloid-negative controls.