Cerebral Amyloid Angiopathy

Introduction

Cerebral amyloid angiopathy (CAA) is a microangiopathy defined by progressive deposition of beta amyloid (Aβ) in the walls of distal cortical and leptomeningeal vessels. The resulting small vessel damage can result in hemorrhage, infarction, and/or chronic hypoperfusion, the sequela of which produce a spectrum of characteristic neuroimaging findings. Although both hereditary and sporadic forms exist, in this chapter, we will focus on sporadic CAA, which is most commonly found in older individuals and is associated with Alzheimer dementia (AD).

Epidemiology, Pathology, and Clinical Presentation

CAA is a frequent neuropathologic finding and fairly common clinical entity in the elderly. Population studies estimate the presence of CAA in approximately 30% of individuals older than 60 years and approximately 55% of patients with dementia. The most severe complication of CAA is hemorrhage. Approximately 20% of spontaneous intracranial hemorrhage in the elderly is attributable to CAA.

CAA results from impaired perivascular lymphatic drainage and failure of elimination of Aβ from the brain with age and AD. Aβ is derived from proteolysis of the amyloid precursor protein, an integral membrane protein found in many tissues but concentrated in the synapses of neurons. Different proteolytic enzymes produce Aβ of varying lengths, solubility, and aggregation capabilities. Under normal conditions, all forms diffuse through the narrow extracellular spaces of the brain parenchyma before entering the bulk flow lymphatic drainage pathways located in the basement membranes of distal cortical and leptomeningeal arterioles and capillaries. These peripheral vessels seem particularly prone to Aβ deposition due to the basic composition of the arterial wall and absence of alternative perivascular lymphatic drainage pathways. Age and certain genetic factors contribute to changes in the basement membrane and hardening of the arterial walls, which disrupts this drainage. In this setting, the longer, insoluble form of Aβ (Aβ42), which tends to aggregate more easily, is more readily deposited in the brain parenchyma, contributing to the formation of senile plaques and AD. The shorter, soluble form (Aβ40), which does not aggregate as easily, can still diffuse through the extracellular matrix but is not easily cleared by the cerebral lymphatics and becomes deposited in the basement membrane, laying the foundation for CAA.

As disease progresses and Aβ accumulates, it disrupts the basement membrane, erodes smooth muscle, and eventually replaces the entire vessel wall, extending into the adventitia ( Fig. 4.1 ). Severe CAA is often accompanied pathologically by obliterative intimal changes, hyaline degeneration, microaneurysmal dilation, and fibrinoid necrosis. The resulting vasculopathy is the basis for CAA pathology, leading to development of acute and chronic hemorrhage, ischemia, and chronic hypoperfusion, any or all of which can be reflected in the computed tomography (CT) and magnetic resonance imaging (MRI).

Clinical and Imaging Features