Alzheimer’s disease (AD) is a devastating disorder that affects the lives of both patients and their loved ones. While it is believed that AD is due to a buildup of amyloid plaques in the brain that eventually lead to the formation of neurofibrillary tangles (NFTs) and result in neurodegeneration, there are many theories that attempt to define the causes of AD. This paper investigates the amyloid and tau theories in more detail, including how these proteins can spread in the brain. It will also take a look into other potential theories that could contribute to AD symptoms such as vascular issues or neuroinflammation. Frontotemporal dementia (FTD) is another form of dementia, albeit much rarer than AD, that is typically characterized by symptoms that follow the opposite progression of AD: behavior and judgement are affected before memory. In addition, FTD is closely related to amyotrophic lateral sclerosis (ALS), a movement disorder that is caused by a loss of motor neurons that results in loss of muscle control. This paper will also examine how FTD and ALS are related, as well as theories behind the potential causes of these disorders. Finally, this paper will examine a patient who exhibits signs and symptoms of both disorders to attempt to determine the potential diagnosis.

The ERK1/2 cell signaling pathway is highly conserved and a prominent regulator of processes like cell proliferation, differentiation, and survival. During nervous system development, the ERK1/2 cascade is activated by the binding of growth factors to receptor tyrosine kinases, leading to the sequential phosphorylation of intracellular protein kinases in the pathway and eventually ERK1 and ERK2, the effectors of the pathway. Well-defined germline mutations resulting in hyperactive ERK1/2 signaling have been implicated in a group of neurodevelopmental disorders called RASopathies. RASopathic individuals often display features such as developmental delay, intellectual disability, cardio-facial abnormalities, and motor deficits. In addition, loss-of-function in ERK1/2 can lead to neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability. To better understand the pathology of these neurodevelopmental disorders, the role of ERK1/2 must be examined during the development of specific neuronal and glial subtypes. In this study, we bred transgenic mice with conditional deletion of ERK1/2 in cholinergic neuronal populations to investigate whether ERK1/2 mediates the survival or activity of basal forebrain and striatal cholinergic neurons during postnatal development. By postnatal day 10, we found that ERK1/2 did not seem to mediate cholinergic neuron number within the basal forebrain or striatum. In addition, we showed that expression of FosB, a neuronal activity-dependent transcription factor and target of ERK1/2, was not yet observed in cholinergic neurons within either of these anatomical regions by P10. Finally, our preliminary data suggested that FosB expression within layer IV of the somatosensory cortex, a target domain for basal forebrain cholinergic projections, also did not appear to be mediated by ERK1/2 signaling. However, since cholinergic neuron development is not yet complete by P10, future work should explore whether ERK1/2 plays any role in the long-term survival and function of basal forebrain and striatal cholinergic neurons in adulthood. This will hopefully provide more insight into the pathology of neurodevelopmental disorders and inform future therapeutic strategies.

Alzheimer’s Disease (AD) is the most prevalent form of dementia and is the sixth leading cause of death in the elderly. Evidence suggests that forms of stress, including prenatal maternal stress (PMS), could exacerbate AD development. To better understand the mechanism linking PMS and AD, we investigated behavior and specific epigenetic markers of the 3xTg-AD mouse model compared to aged-controls in offspring of stressed mothers and non-stressed mothers.