Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer's disease pathology.

Alzheimer's disease (AD) is the most common cause of dementia worldwide, but the molecular and cellular mechanisms underlying cognitive impairment remain poorly understood. To address this, we generated a single-cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from postmortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment. Our analyses identified AD-pathology-associated alterations shared between excitatory neuron subtypes, revealed a coordinated increase of the cohesin complex and DNA damage response factors in excitatory neurons and in oligodendrocytes, and uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology. Furthermore, we identified selectively vulnerable somatostatin inhibitory neuron subtypes depleted in AD, discovered two distinct groups of inhibitory neurons that were more abundant in individuals with preserved high cognitive function late in life, and uncovered a link between inhibitory neurons and resilience to AD pathology.

Frequency of diencephalic syndrome in NMOSD.

BACKGROUND: Diencephalic region of the brain harbors sites with a considerable amount of aquaporin-4 expression. Neuromyelitis optica spectrum disorder (NMOSD) primarily involves autoimmune processes against this molecule. However, little is known about the frequency of symptoms of diencephalic involvement in NMOSD patients. OBJECTIVE: To investigate the frequency of symptoms of diencephalic involvement in NMOSD patients and describe the associated characteristics in patients presenting such symptoms. MATERIALS AND METHODS: This retrospective cohort included 145 NMOSD patients (39 males and 106 females) who visited Isfahan Multiple Sclerosis Center from January 2013 to February 2020 for approximately 61 months. Demographic and clinical information of patients and findings from radiological and serological investigations were retrieved. RESULTS: The frequency of diencephalic involvement in NMOSD patients was 3.4% (five cases). Diencephalic syndrome-associated symptoms observed in this cohort consisted of narcolepsy (n = 2; 40%), hypotension (n = 1; 20%), amenorrhea (n = 1; 20%), and syndrome of inappropriate antidiuretic hormone secretion (n = 1; 20%). These manifestations responded well to NMOSD-associated treatments, i.e., rituximab and azathioprine. CONCLUSION: Although rarely manifested through symptoms suggestive of diencephalic involvement, NMOSD should be considered when encountering patients with the diencephalic syndrome to identify the primary cause of these manifestations.