Why Does Neuroplasticity Fail to Rescue the Alzheimer’s Brain? Biological Brakes and Philosophical Reflections

Will your competent? doctor contact stroke leadership to get research going to solve this problem? Nothing will occur since there is NO STROKE LEADERSHIP and your doctor won't even attempt to create stroke leadership. Your incompetent? doctors didn't get further research done on myelin-associated glycoprotein in the last decade, did they? So, they proved THEIR COMPLETE INCOMPETENCE!

myelin-associated glycoprotein (1 post to May 2015)

 Why Does Neuroplasticity Fail to Rescue the Alzheimer’s Brain? Biological Brakes and Philosophical Reflections

Beyza Aksu1 and Bekir Faruk Erden 2 * 1Department of Health Care Services, Division of Podiatry, Vocational School of Health Services, Kocaeli University, Kocaeli, Türkiye 2Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Türkiye

Abstract ISSN: 2692-448X DOI: http://dx.doi.org/10.17352/aadc Received: 22 September, 2025 Accepted: 01 October, 2025 Published: 02 October, 2025 *Corresponding author: Bekir Faruk Erden, Department of Pharmacology, Kocaeli University Medical Faculty, Kocaeli, Türkiye, E-mail: berden@kocaeli.edu.tr Keywords: Alzheimer’s disease; Neuroplasticity; Biological brakes; Synaptic dysfunction; Cognitive resilience Copyright License: © 2025 Aksu B, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://www.neuroscigroup.us Alzheimer’s disease represents a paradox in which the brain’s intrinsic capacity for neuroplasticity fails to prevent progressive decline. 

Unlike stroke, where intact circuits can reorganize and restore function, AD is marked by diffuse degeneration and active molecular brakes that suppress recovery. This article reviews the dual barriers of myelin-associated inhibitors and chronic neuroinflammation, and further considers the philosophical implications of conditional plasticity. Therapeutic strategies must therefore aim both to release inhibitory signaling pathways and to support the structural substrate of cognition. Alzheimer’s disease embodies a striking paradox: the human brain’s famed capacity for neuroplasticity simply fails when it is needed most. After a stroke, patients can relearn to walk or speak; cortical maps reshape, and function returns. Yet in Alzheimer’s disease (AD), this restorative force does not emerge. The obvious question arises-why? 

We argue that the explanation lies in the “brakes” of neuroplasticity. Far from being a free-flowing repair system, the adult brain is actively restrained by molecular gatekeepers. Myelin-associated inhibitors such as Nogo-A, myelin associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp) activate the Nogo receptor, triggering RhoA/ROCK signaling to collapse neurites and block sprouting [1]. At the same time, chronic neuroinflammation in AD amplifies the blockade: cytokines such as interleukin-1 and tumor necrosis factor- impair long-term potentiation and memory consolidation [2]. In addition, recent evidence shows that network instability and the collapse of homeostatic mechanisms further restrict adaptive remodeling [3]. This dual inhibition explains the paradox. 

Stroke represents an acute focal insult, sparing networks that can reorganize. Alzheimer’s, however, is a slow and diffuse degeneration— eroding not only neurons but also the scaffolds on which plasticity depends. Thus, the very conditions that foster recovery in stroke are absent in AD. Beyond biology, this raises a philosophical challenge. Neuroplasticity is not a universal healing principle; it is conditional. In some diseases, the brain is permitted to rescue itself; in others, it is forbidden. The stroke brain benefits from plasticity; the Alzheimer’s brain is locked out of its own defense. This perspective forces us to abandon overly romantic notions of neuroplasticity and face its limits. For therapy, this means that simply “boosting plasticity” in AD will not suffice. Instead, strategies must combine two steps: first, releasing the brakes (for example, using ROCK inhibitors or anti-Nogo agents) [4]; second, nurturing the substrate with trophic factors, enriched environments, or cognitive interventions [5,6]. Clinical neuroscience has increasingly emphasized that harnessing neuroplasticity requires both molecular interventions and structured rehabilitation paradigms [7]. Without lifting the restraints, plasticity remains a locked door in a collapsing house.