Background: Previous studies have used immunohistology to demonstrate Alzheimer's disease (AD) characteristic accumulation of amyloid-␤ (A␤) in the retina of AD patients, a finding indicating retina examination as a potential diagnostic tool for AD pathology. Objective: To further explore this idea by investigating whether levels of A␤ 42 and A␤ 40 in retina are associated with corresponding levels in hippocampus, neuropathological assessments, apolipoprotein E (APOE) genotype, and levels of islet amyloid polypeptide (IAPP). Methods: Levels of high molecular weight (HMW) A␤ 42 , A␤ 40 , and IAPP in ultra-centrifuged homogenates of retina and hippocampus from patients with AD, multiple sclerosis, AD with Lewy bodies, and non-demented controls were analyzed using Mesoscale Discovery electrochemiluminescence technology employing immunoassay and enzyme-linked immunosorbent assay. Results: Higher levels of retinal and hippocampal A␤ 42-HMW , A␤ 40-HMW , and IAPP-HMW were found in individuals with high neuropathological scores of A␤ plaques and in individuals carrying the APOE 4 allele. The retinal levels of A␤ 42-HMW and A␤ 40-HMW correlated with corresponding levels in hippocampus as well as with neurofibrillary tangles (NFT) and A␤ scores. Retinal IAPP-HMW correlated with retinal levels of A␤ 42-HMW and with NFT and A␤ scores. Conclusion: These results show that different isoforms of A␤ can be detected in the human retina and moreover support the growing number of studies indicating that AD-related pathological changes occurring in the brain could be reflected in the retina.

Amylin, a pancreatic β-cell-derived peptide hormone, forms inclusions in brain microvessels of patients with dementia who have been diagnosed with type 2 diabetes and Alzheimer’s disease. The cellular localization of these inclusions and the consequences thereof are not yet known. Using immunohistochemical staining of hippocampus and parahippocampal cortex from patients with Alzheimer’s disease and non-demented controls, we show that amylin cell inclusions are found in pericytes. The number of amylin cell inclusions did not differ between patients with Alzheimer’s disease and controls, but amylin-containing pericytes displayed nuclear changes associated with cell death and reduced expression of the pericyte marker neuron-glial antigen 2. The impact of amylin on pericyte viability was further demonstrated in in vitro studies, which showed that pericyte death increased in presence of fibril- and oligomer amylin. Furthermore, oligomer amylin increased caspase 3/7 activity, reduced lysate neuron-glial antigen 2 levels and impaired autophagy. Our findings contribute to increased understanding of how aggregated amylin affects brain vasculature and highlight amylin as a potential factor involved in microvascular pathology in dementia progression.

BACKGROUND Among patients with well differentiated papillary thyroid carcinoma who generally have an excellent prognosis and a near‐normal lifespan, there exist subsets of patients who have significant risk for morbidity and mortality from this disease. It is important to define the patterns of disease progression and the clinical outcome of such patients to develop effective surveillance and treatment strategies. Patients with recurrence after surgery and therapeutic administration of radioactive iodine (RAI) for papillary thyroid carcinoma represent one such subset of high‐risk patients. METHODS At The University of Texas M. D. Anderson Cancer Center, 65 patients with papillary thyroid carcinoma were diagnosed between 1970 and 1990. Their medical records were reviewed with particular attention to disease recurrence and outcome as well as RAI imaging and treatment. RESULTS Following diagnosis and initial therapy, 19 patients died from thyroid carcinoma after a median of 64 months; 34 had no evidence of disease for a median of 112 months of available follow‐up; and 7 are alive with disease 61 to 153 months after diagnosis. Cervical lymph node metastases were present in 41 patients and extrathyroidal or extranodal tumor invasion was seen in 25 patients at the time of initial surgery; distant metastases (lung, bone, brain, liver, and adrenal) developed later in 18 patients. RAI uptake by recurrent tumor deposits in the neck was seen most frequently in patients with no direct invasion of adjacent tissues but with recurrence limited to cervical lymphadenopathy; this group of patients was the most likely to become clinically and radiologically disease free. RAI generally did not concentrate in invasive cancers with extrathyroidal or extranodal extension in the neck; patients with this type of invasive carcinoma were also more likely to die from the disease. CONCLUSIONS We suggest that among patients with recurrent papillary thyroid carcinoma, invasive cancers are less likely to concentrate RAI, whereas patients with disease confined to lymph nodes are more likely to have RAI‐avid tumors and to benefit from RAI therapy. Cancer 1996;78:493‐501.

SummaryThe population of brain pericytes, a cell type important for vessel stability and blood brain barrier function, has recently been shown altered in patients with Alzheimer's disease (AD). The underlying reason for this alteration is not fully understood, but progressive accumulation of the AD characteristic peptide amyloid‐beta (Aβ) has been suggested as a potential culprit. In the current study, we show reduced number of hippocampal NG2+ pericytes and an association between NG2+ pericyte numbers and Aβ1‐40 levels in AD patients. We further demonstrate, using in vitro studies, an aggregation‐dependent impact of Aβ1‐40 on human NG2+ pericytes. Fibril‐EP Aβ1‐40 exposure reduced pericyte viability and proliferation and increased caspase 3/7 activity. Monomer Aβ1‐40 had quite the opposite effect: increased pericyte viability and proliferation and reduced caspase 3/7 activity. Oligomer‐EP Aβ1‐40 had no impact on either of the cellular events. Our findings add to the growing number of studies suggesting a significant impact on pericytes in the brains of AD patients and suggest different aggregation forms of Aβ1‐40 as potential key regulators of the brain pericyte population size.