The Role of Myelin and Large-Scale Brain Networks in Alzheimer's Disease and Cognition

Flashcards covering the cellular substrates of brain networks, myelin dynamics in health and Alzheimer's disease, and the relationship between cognitive learning and adaptive myelination.

What is the "reazione nera" (black reaction)?

A silver-chromate impregnation technique developed by Camillo Golgi in 1873 that selectively labels a sparse subset of neurons and glial cells in their entirety against an unstained background.

How did Santiago Ramón y Cajal's findings refute the reticular theory?

He used the Golgi method to demonstrate that the brain is an assembly of discrete, individually bounded cells (the neuron doctrine) that communicate through specialized contact points called synapses.

What is the difference between structural and functional connectivity?

Structural connectivity refers to the physical white matter tracts linking brain regions, while functional connectivity refers to the statistical dependence (temporal correlation of BOLD signals) between the activity of spatially separated regions.

What is the physiological basis of the BOLD signal in fMRI?

It relies on neurovascular coupling; increased neural activity leads to a rise in local cerebral blood flow that exceeds oxygen consumption, reducing deoxygenated (paramagnetic) hemoglobin and increasing the MRI signal.

What are the core regions of the Default Mode Network (DMN)?

The medial prefrontal cortex ($mPFC$), posterior cingulate cortex ($PCC$), and the precuneus.

How does myelination facilitate saltatory conduction?

By insulating axonal segments and concentrating voltage-gated $Na^+$ channels at the nodes of Ranvier, allowing action potentials to leap between nodes and increasing conduction velocity up to 100-fold.

What metabolic support do oligodendrocytes provide to axons?

They supply metabolic substrates such as pyruvate and lactate through monocarboxylate transporters ($MCT1$).

What markers identify oligodendrocyte precursor cells ($OPCs$)?

The proteoglycan $NG2$ and the receptor tyrosine kinase $PDGFR\textnormal{α}$.

What is the biphasic trajectory of DMN connectivity observed in the $App^{NL-G-F/NL-G-F}$ mouse model?

The network moves from early hyper-synchrony during initial plaque deposition to late-stage hypo-synchrony as amyloid burden advances.

Which hippocampal subregions showed demyelination as early as 7 months in the Alzheimer's mouse model?

The $CA3$ and the dentate gyrus ($DG$).

How does amyloid pathology affect age-dependent myelin maturation?

It arrests the normal trajectory of age-dependent myelin maturation observed in healthy controls rather than merely accelerating demyelination.

What was the relationship between myelin and DMN strength in healthy ($App^{NL/NL}$) mice?

Myelin basic protein ($MBP$) coverage positively predicted $DMN$ amplitude in the anterior cingulate cortex ($ACC$) and $CA3$, a relationship that was absent in animals with amyloidopathy.

What does a reduction in $T1$ relaxation time on quantitative MRI typically indicate?

An increase in myelin content.

What is the Trial-Unique Delayed Non-Matching-to-Location ($TUNL$) task?

A touchscreen-based behavioral test that assesses spatial working memory and pattern separation without a motor learning component.

What did the conditional knockout of the Myelin Regulatory Factor ($Myrf$) reveal about cognitive learning?

It established that new myelination is a biological requirement for the acquisition of spatial working memory.

What is the ATN framework for Alzheimer's disease biomarkers?

A classification system based on three categories: amyloid-beta deposition ($A$), pathological tau ($T$), and neurodegeneration ($N$).

Which genetic allele is the strongest risk factor for late-onset Alzheimer's disease?

The apolipoprotein E epsilon 4 allele ($APOE4$).

What is the "Swedish mutation" in the context of the $App$ knock-in model?

A mutation designated as $KM670/671NL$ that increases total amyloid-beta production.

Why were yoked control groups used in the $TUNL$ experiments?

To isolate cognitive rule learning from non-specific demands like reward consumption, motor movement, and sensory stimulus exposure.

In addition to the $mPFC$ and hippocampus, which other regions showed $T1$ reductions after cognitive training?

The amygdala, ventral tegmental area ($VTA$), substantia nigra ($SN$), parietal cortex, and cerebellum.