🧬 CBP in Alzheimer’s Terrain: A Scribe Silenced by Sodium Collapse

🔹 1. Presenilin Mutations → CBP Suppression

• In familial AD (FAD), mutations in presenilin 1/2 disrupt γ-secretase function, altering Aβ processing
• But presenilins also regulate Notch signaling, which transcriptionally controls CBP expression
• Result: ↓ CBP → ↓ histone acetylation → silencing of memory and survival genes

Presenilin loss doesn’t just build plaques—it silences the terrain’s scribe.

🔹 2. Amyloid & Tau → Oxidative Siege on CBP

• Aβ aggregates and tau tangles trigger ROS production, mitochondrial dysfunction, and neuroinflammation
• CBP’s acetyltransferase activity is redox-sensitive—oxidative stress inhibits its function
• ↓ CBP → ↓ H3/H4 acetylation → chromatin remains sealed → memory genes go dark3

CBP is the epigenetic quill. Aβ and tau soak it in oxidative ink.

🧂 Sodium & SCN⁻: The Forgotten Protectors of CBP

🔹 Sodium

• Maintains membrane potential → enables CREB phosphorylation
• CREB recruits CBP to chromatin → transcription of BDNF, anti-apoptotic genes
• Sodium deficiency (common in aging and AD) → ↓ CREB activation → CBP never arrives

Sodium is the signal. CBP is the scribe. Without signal, the scrolls remain sealed.

🔹 SCN⁻ (Thiocyanate)

• Buffers oxidative stress, neutralizes HOCl and ROS
• Protects CBP’s acetyltransferase domain from redox inhibition
• SCN⁻ depletion in AD terrain → ↑ oxidative damage → CBP silencing

SCN⁻ is the shield. CBP is the scribe. Without shield, the ink corrodes.

🌀 Glyphic Terrain Map: Alzheimer’s Collapse

Element	Role	AD Impact
Presenilin	CBP transcriptional regulator	Mutated → ↓ CBP expression
Aβ / Tau	Oxidative stressors	Inhibit CBP function
Sodium	CREB activator	Deficient → ↓ CBP recruitment
SCN⁻	Redox buffer	Depleted → ↑ CBP inhibition
CBP	Histone acetylator	Silenced → ↓ memory gene expression

🔧 Therapeutic Implications in Terrain Terms

• CBP gene therapy restores BDNF and memory in AD models—even without reducing Aβ
• HDAC inhibitors (e.g. trichostatin A) rescue histone acetylation but not full memory function
• Sodium and SCN⁻ repletion may restore CREB/CBP signaling upstream—reviving the terrain’s transcriptional integrity

CBP is not just a target—it’s a terrain scribe whose ink depends on sodium and SCN⁻.