In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration.

Cross-sectional studies raise the possibility of protective relationships between, or a common mechanism underlying, the development of dementia of the Alzheimer type (DAT) and cancer. Using a prospective longitudinal design, the authors found that the risk of developing cancer is less among participants with DAT vs nondemented participants (p < 0.001) and that the risk of developing DAT may be less for participants with a history of cancer (p = 0.060).

HDDD2 is an FTLD-U caused by a missense mutation in the PGRN gene that cosegregates with the disease and with the disease haplotype in at-risk individuals. This mutation is the first reported pathogenic missense mutation in the signal peptide of the PGRN gene causing FTLD-U. In light of the previous reports of null mutations and its position in the gene, two possible pathological mechanisms are proposed: (1) the protein may accumulate within the endoplasmic reticulum due to inefficient secretion; and (2) mutant RNA may have a lower expression because of degradation via nonsense-mediated decay.

Cancer and Alzheimer’s disease (AD) are two common disorders for which the final pathophysiological mechanism is not yet clearly defined. In a prospective longitudinal study we have previously shown an inverse association between AD and cancer, such that the rate of developing cancer in general with time was significantly slower in participants with AD, while participants with a history of cancer had a slower rate of developing AD. In cancer, cell regulation mechanisms are disrupted with augmentation of cell survival and/or proliferation, whereas conversely, AD is associated with increased neuronal death, either caused by, or concomitant with, beta amyloid (Aβ) and tau deposition. The possibility that perturbations of mechanisms involved in cell survival/death regulation could be involved in both disorders is discussed. Genetic polymorphisms, DNA methylation or other mechanisms that induce changes in activity of molecules with key roles in determining the decision to “repair and live”- or “die” could be involved in the pathogenesis of the two disorders. As examples, the role of p53, Pin1 and the Wnt signaling pathway are discussed as potential candidates that, speculatively, may explain inverse associations between AD and cancer.

The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients.

Dementia is becoming increasingly prevalent in Latin America, contrasting with stable or declining rates in North America and Europe. This scenario places unprecedented clinical, social, and economic burden upon patients, families, and health systems. The challenges prove particularly pressing for conditions with highly specific diagnostic and management demands, such as frontotemporal dementia. Here we introduce a research and networking initiative designed to tackle these ensuing hurdles, the Multi-partner consortium to expand dementia research in Latin America (ReDLat). First, we present ReDLat's regional research framework, aimed at identifying the unique genetic, social, and economic factors driving the presentation of frontotemporal dementia and Alzheimer's disease in Latin America relative to the US. We describe ongoing ReDLat studies in various fields and ongoing research extensions. Then, we introduce actions coordinated by ReDLat and the Latin America and Caribbean Consortium on Dementia (LAC-CD) to develop culturally appropriate diagnostic tools, regional visibility and capacity building, diplomatic coordination in local priority areas, and a knowledge-to-action framework toward a regional action plan. Together, these research and networking initiatives will help to establish strong cross-national bonds, support the implementation of regional dementia plans, enhance health systems' infrastructure, and increase translational research collaborations across the continent.

There is now extensive evidence that amyloid-␤ peptide is toxic to neurons and that its cytotoxic effects can be attributed to a domain corresponding to amyloid-␤ 25-35, GSNKGAIIGLM. We have shown recently that the serine proteinase inhibitor ( I-peptide 105Y (SIPPEVKFNK-PFVYLI), based on the sequence of a candidate receptor binding domain in the carboxyl-terminal tail of ␣1-AT. This peptide mediated an increase in synthesis of ␣1-AT in monocytes and human hepatoma HepG2 cells, and binding studies showed that it described a receptor with a K d of ϳ40 nM and ϳ450,000 plasma membrane receptors per cell (1). Binding of radioiodinated peptide 105Y was blocked by unlabeled ␣1-ATelastase complexes, and binding of radioiodinated ␣1-AT-elastase complexes was blocked by unlabeled peptide 105Y (1), thus providing evidence that SEC-R was indeed a binding site for ␣1-AT-elastase complexes.SEC-R is now known to have a ligand-binding subunit of ϳ84 kDa (2) which is expressed on a diverse array of cell types. It mediates endocytosis and intracellular degradation of ␣1-ATelastase complexes (3) and mediates directed migration of neutrophils toward this ligand (4). In studies designed to define the minimal requirements for binding, we showed that a pentapeptide at the carboxyl-terminal aspect of peptide 105Y was sufficient for binding to SEC-R (5). This pentapeptide is highly conserved among members of the serpin supergene family. Several of the other serpins, such as ␣1-antichymotrypsin, antithrombin III, heparin cofactor II and, to a lesser extent, C1 inhibitor and plasminogen activator inhibitor I, when in complex with their cognate serine protease, compete for binding to SEC-R (1, 6). A similar pentapeptide sequence was identified in several tachykinins and amyloid-␤ peptide. In fact, competitive binding studies have shown that: (i) soluble amyloid-␤ peptide binds to SEC-R on HepG2 cells (2); (ii) soluble amyloid-␤ peptide binds to SEC-R on neutrophils, mediating chemotactic activity and conferring homologous desensitization to the chemotactic activity of peptide 105Y (4); (iii) soluble amyloid-␤ peptide binds to SEC-R on neuronal cells (7); (iv) the region corresponding to amyloid-␤ peptide 25-35, and particularly amyloid-␤ 31-35, is critical for binding to SEC-R on any of these cell types (7); (v) amyloid-␤ 1-39, amyloid-␤ 1-40, and amyloid-␤ 1-42, when prepared in soluble form in Me 2 SO, present this binding domain to SEC-R to an equivalent extent (7); (vi) SEC-R mediates endocytosis and catabolism of soluble amyloid-␤ peptide in hepatocytic and neuronal cell types (7).

The MoCA-S1-2 is a short, easy-to-use, and useful test for diagnosing aMCI and mild dementia.