Abstract: Alzheimer’s disease (AD) has been traditionally viewed as a purely neuronal pathology, marked by synaptic loss , amyloid-β(Aβ) accumulation, tautangles , neuroinflammation, and metabolic imbalance. Over the past two decades, cerebrovascular dysfunction has emerged as both a co-initiator and an amplifier of AD pathology. Structural and functional perturbations within the neurovascular unit (NVU) — a dynamic interface of vascular, glial, and neuronal cells that coordinates cerebral blood flow (CBF), maintains blood–brain barrier (BBB) integrity, and regulates neuronal and synaptic activity —can precede overt cognitive symptoms and contribute to the collapse of cerebral homeostasis (Zlokovic et al., 2011; Luo et al., 2022). Accordingly, neurodegeneration and cerebrovasculopathy evolve in parallel and may reinforce each other, acting either independently and/or in synergy with Aβ accumulation. This is particularly evident in regions such as the brainstem, where the vascular architecture is uniquely vulnerable: paramedian perforating vessels arise directly from major arterial trunks, lack collateralization, and possess thin walls prone to hypertension-induced damage. These features expose these regions to elevated shear stress, spontaneous microbleeds and ischemic injury, contributing to their selective vulnerability in aging and dementia. In AD, such vascular fragility may underlie the early degeneration of the isodendritic core nuclei and the dysfunction of their projection fields (Zaccone et al., 2025).