ALZFORUM is a long-running, industry-supported site covering Alzheimer's research, and the staff there turn out a good line in explanatory and popular science articles on the topic. This is something that we need a lot more of in the field of aging research, and especially for those portions of the field focused on SENS or SENS-like strategies of damage repair. Efforts like LIFEmag, the Longevity Reporter, the Rejuvenation Biotechnology Update quarterly emails to supporters of the Methuselah Foundation and SENS Research Foundation, and the publications of the Healthspan Campaign and similar are steps in the right direction, but there is still a sizable gap to be filled here.
Some of that gap is, I think, conceptual. People who are developing the symptoms of Alzheimer's - and their supporters and their caregivers - will do exactly what everyone else faced with currently intractable medical issues does: go online, network, find a community, read up on research. People suffering from aging, which is to say everyone, don't really exhibit all that much of the same behavior, however. Convincing the rest of the world to think of aging itself as a medical condition, amenable to near-future treatment, rather than a fact of life is perhaps still a hurdle to be overcome. In any case, today I'll point out a couple of articles recently published at ALZFORUM; see what you think:
The blood-brain barrier shields the brain from potentially harmful things, and some findings have suggested that this protective border weakens with age or disease. However, a study now reports that the barrier remains largely intact in multiple mouse models of neurodegenerative disease. The researchers also found that brains from healthy aging people bore the scars of just as many barrier breaches as those from Alzheimer's disease (AD) patients. This study contradicts previous work that has called disruption of the blood-brain barrier (BBB) both a cause and a consequence of AD pathology.
Researchers wanted to formally test the idea that AD disrupts the BBB. They are developing a strategy to smuggle therapeutic antibodies across the brain's border, hence evidence of an intact barrier would further support the need for such a trafficking route. The researchers previously developed bispecific antibodies, which recognize a different target with each of their two arms. While one arm recognizes BACE1, the other latches on to the transferrin receptor (TfR) expressed on endothelial cells lining the barrier, which then transport the antibody across via transcytosis. In plaque-ridden, 10- to 13-month-old PS2-APP mice, the researchers found that, as in wild-type mice, only the bispecific TfR antibody crossed the barrier efficiently, while BACE1 or control antibodies remained largely outside. This indicated that a barrier disruption large enough to let antibodies across did not occur in these AD mice. The same held true for two transgenic mouse models expressing disease-associated forms of human tau despite extensive tauopathy and neurodegeneration.
The authors' conclusion that the blood-brain barrier remains largely intact across models of neurodegenerative disease and in humans with AD contradicts many studies using differing techniques that say otherwise. What do results from AD mouse models say about the state of the BBB in human disease? Maybe the import of antibodies is limited because one big difference between animal models and human AD is the presence of cerebral amyloid angiopathy (CAA). In some people, the vascular amyloid deposits of CAA cause vessels to bleed, but most mouse models have no CAA.
Behind every successful neuron, there is a support crew of glia. Stem cell researchers are aiming to replace both types of cell in an effort to slow neurodegenerative disease. The defining characteristic of neurodegenerative disease is the death of neurons, and researchers have long searched for ways to either replace the fallen cells or bolster support for those that remain. Stem cell therapy offers opportunities to try both. Scientists have developed protocols to transform stem cells or induced pluripotent stem cells (iPSCs) into neurons of various persuasions, or into the glial cells that support them.
Another approach is to skip the complexity of the stem cell altogether and directly deliver trophins such as brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF). The latter has a long history. In 2001, researchers delivered NGF to people with probable AD by injecting directly into the striatum either patient-derived fibroblasts engineered to pump out NGF, or adeno-associated virus (AAV) expressing NGF. Recently, the scientists reported postmortem results from 10 patients who died between one and 10 years later. The researchers observed neurons undergoing a growth spurt - putting out axonal projections and expressing key signaling molecules - in the areas near the injection. In the viral gene therapy recipients, both healthy neurons and degenerating cells riddled with tau tangles expressed NGF, indicating that even sickly neurons retain the capacity to produce trophic factors. While the results did not reveal whether the trophic support slowed the pace of AD in these patients, they suggest that when such therapy is delivered, neurons respond.
Viral delivery of BDNF has shown promise in rodent models of neurodegenerative disease as well as in aging primates. However, the treatment is still in its preclinical stages as researchers grapple with the challenge of efficiently delivering the trophin to specific regions in the brain. Some researchers believe that the factors might work best when delivered by professionals (i.e., by glial cells that normally produce them). This was tried this in ASO mice, a model of dementia with Lewy bodies (DLB) that overexpresses human α-synuclein. These animals are riddled with Lewy bodies and develop both motor and cognitive deficits. The researchers transplanted neural stem cells (NSCs) derived from normal mice directly into the striata of 12-month-old ASO mice. They found that the transplanted cells differentiated into astrocytes and oligodendrocytes, and six weeks after the injection had migrated throughout the striatum and even into the neighboring cortex and amygdala. The transplanted cells restored the animals' deteriorating motor function, as well as learning and memory.